Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism

*Nimsi Campos-Xolalpa, Julia Pérez-Ramos, Ana Esquivel-Campos, Cuauhtemoc Pérez-González, Leonor Sánchez-Pérez and Salud Pérez-Gutiérrez*

## **Abstract**

Cancer is a group of related diseases in which there is uncontrolled cell growth that spreads to the surrounding tissues and damages them. Cancer remains the disease with the leading cause of death worldwide, and incidence and mortality are increasing rapidly. The main cancer treatment is chemotherapy; however, the compounds used in this treatment have serious side effects for this reason, is necessary to develop new therapeutic strategies. Natural products are an excellent pharmacological alternative for the treatment of cancer and infections. In search of new compounds with cytotoxic and antimicrobial activity, we have found quinones that have a high pharmacological potency in the treatment of these health problems. Quinones are an aromatic system of one or diketone and are mainly isolated from plants, fungi, bacteria, and other organisms. These compounds are secondary metabolites derived from the oxidation of hydroquinones; they include benzoquinones, naphthoquinones, anthraquinones, and polyquinones. This review summarizes the activity of 152 anticancer and 30 antimicrobial quinones.

**Keywords:** quinones, cancer, cytotoxic, antimicrobial, natural product

## **1. Introduction**

Cancer is a group of a collection of related diseases where there is uncontrolled cell growth and spread into surrounding tissues, producing damage to them. In many cases, these cells form tumors and some cancer cells travel through the lymphatic system or blood to other places of the body and form new tumors.

Cancer remains the disease with major cause of death globally. In 2018, there were reported about 18 million new cases of cancer [1] and approximately 9.6 million deaths from this disease [2]; in addition, all over the world, the incidence and mortality of cancer are increasing. The risk of incidence of cancer is associated with age, infections, and human habits like poor diet, consumption of alcohol, tobacco, and others [3]; also, there are genetic predisposition and immune conditions [4].

Diseases due to the infections of bacteria and fungi are a very important health problem throughout the world. In 2019, the incidence of infection transmitted by

food and water increased. The treatment of infection by bacteria is the administration of antibiotics; however, these drugs have been losing effectiveness because there is increased bacterial drug resistance [5]. The main causes of bacterial resistance are unnecessary prescriptions [6] and the unregulated antibiotics sale in many countries, leading to inadequate and unnecessary consumption [7]. Then, infections treatments become more expensive and have less effective.

From ancient times, natural products have been used in the treatment of different diseases, for example, in Egypt around 1550 BC, the "Ebers Papyrus" reported the use of 700 drugs [8]. Nowadays, natural products are an important source of compounds with great potential for the treatment of infections and different forms of cancer [9].

Quinones are an important family of natural products. They have a variety of biological effects, such as anticancer and antimicrobial activities [10, 11]. The 1,4 naphthoquinones, since ancient times, have been used as cosmetics for coloring skin, as well as the treatment of some diseases. These compounds have several activities like anti-inflammatory, antiviral, anticancer, and antibacterial, among others.

For example, juglone and plumbagin show an antimicrobial effect on bacteria and fungi, and they are defensive compounds in the plant. Cytosporaquine A-D and physcion exhibited cytotoxic activity against several human cell cancer lines.

The cytotoxic and antimicrobial activities of 1,4 naphthoquinones are due mainly to two carbonyl groups present in these compounds, which can accept one or two electrons to form a semiquinone radical or di-anion species and for their acid–base properties [10].

The present review focuses on the anticancer and antimicrobial activities of 182 quinones isolated from natural sources in the last 5 years (**Tables 1** and **2**).

## **2. Anticancer and antimicrobial activity of quinones obtained from plants, animals, and microorganisms**

The incidence of cancer has increased; in 2018, around 9.6 million deaths in the world were due to this disease. The drugs used in chemotherapy have side effects and the cancer cells can have resistance to these drugs. Therefore, the study of new molecules with anticancer activity has become important.

Infectious diseases are an international health public problem, especially in undeveloped countries. For the treatment of these diseases are used antibiotics; however, several microorganisms present resistance to these drugs.

The search for new compounds with these activities has become important. Plants, marine organisms, fungi, and bacteria are natural sources to obtain substances with pharmacological effects.

Quinones are natural products with different pharmacological activities, such as anticancer and antimicrobial effects. These compounds can be obtained by synthesis or the structure modified to increase their activity.

This chapter shows the revision of the literature generated in the last 5 years of quinones isolated from 65 plant species, bacteria, fungi, algae, or sponges. The plants were the most different species studied, followed by fungi with 10 species, Streptomyces with 4 strain investigated, and bacteria with only one studied. Nowadays, the study of marine organisms has become more important, with 3 species of sponges studied and from which these compounds have been isolated, and there was 1 scorpion studied.

The cytotoxic properties of isolated quinones in the period 2015 to 2020 were mainly determined by in vitro and in vivo studies. This was due to some factors such as the sensitivity of these tests and the consumption of small amounts of

**Quinona/ Natural origin (plants, animals,**

**29**

**Structure**

**Activity or model where it was tested**

 **Results**

**Ref.**

**microorganisms)**

**Plants**

7-(30,40-dihydroxy-benzene)-2,3-dimethoxy-

MTT assay

IC50 (μM)

[12]

19.68

28.71

13.75

IC50 μM HL-60 HepG2 BGC-823

(1) 18 48.2

(2) 8.77 38.6

(3) 8.79 43.08

(4) 7.60 40.10

(5) 11.65 > 100

 A2780

[13]

*DOI: http://dx.doi.org/10.5772/intechopen.95598*

 24

 9.70

 10.63

 10.40

 13.07 10.58

 14.50

*Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism*

 15.60

 14.48

 20

Hela

HepG2

K562

MTT assay

1,4-naphthoquinone.

*Ajania salicifolia*

2-hydroxy-5-ethoxy-3-nonyl-1,4-benzoquinone

(1).

5-

*O*-butyl-embelin

5-O-methylembelin

5-O-methyl-rapanone

5-O-ethylembelin

*Aegiceras*  Aloesaponarin

Aloesaponarin

*Aloe* 

*megalacantha*

 I (2).

 II (1).

CAF

IC50 μM

[14]

(1) 0.98

(2) 16

KB-3-1

*corniculatum*

 (5).

 (4).

 (3).

 (2).

(ajaniquinone).


*Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism DOI: http://dx.doi.org/10.5772/intechopen.95598*


**Quinona/ Natural origin (plants, animals,**

**31**

**Structure**

**Activity or model where it was tested**

WST-1 cell viability assay

HepG2

MTT assay MDA-MB231

4 T1 MDA-MB231

HCT-116

MTT assay

HL-60

Western blotting flow cytometry D gel

MTT assay MDA-MB231

4 T1 Immunofluorescence

Experiments *in vivo*

MHTBDE

Huh7

 microscopy

electrophoresis

 **Results** IC50 μM

2

IC50 μM 24 h 48 h 72 h

9.11 3.34 1.83 4.98 2.61 1.74

IC50 μg/mL

72 h 80.2

24.6

IC50 μM

[21]

[19]

[22]

*Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism*

3.83 at 48 h Induced apoptosis in HL-60

strong alteration in cell proteome

ERP57 is downregulated

IC50 μM

24 h 48 h 72 h

4.48 2.31 1.13 1.79 1.02 0.83 shikonin-mediated

signaling via increased levels of GSK-3β in MDA-

MB-231 cells Shikonin inhibits lung metastasis and

signaling in NOD/SCID

MDA-MB-231

IC50

5 X106

M

 cells.

 mice inoculated with

β-catenin

 suppression

 of

β-catenin

 by shikonin

overexpressed

 in AML cells and is

**Ref.**

[18]

[19]

[20]

*DOI: http://dx.doi.org/10.5772/intechopen.95598*

**microorganisms)**

Acetylshikonin

*Lithospermum*

*Onosma visianii*

Shikonin

*Lithospermum*

Different species of

*erythrorhizon*.

*Boraginaceae* family

*erythrorhizon*


*Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism DOI: http://dx.doi.org/10.5772/intechopen.95598*


**Quinona/ Natural origin (plants, animals,**

**33**

**Structure**

**Activity or model where it was tested**

 **Results**

0.27

0.98

0.07

0.06

1.01

67.66

Reduced mRNA levels of MTOR and BCL2, and it

did not affect the expression of

genes.

IC50 μM

[29]

[31]

[32]

*Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism*

66.3

99.31

77.28

73.63

37.57

71.7

>148.15

Suppression

perturbation

ultimately,

cell death in B16F10 cells. This result suggests that the

downregulation

negative effects on

cancer cell growth Showed higher cytotoxic effects

Induced apoptosis and necrosis

the caspase-3 activation pathway decreased the activation of AKT in all tumor cells, induction of reversible damage (DNA).

Changed the Levels of BAX and BCL-2

Inhibited AKT.

independent

 of

 and emodin treatment has

 exacerbate

emodin-induced

 apoptotic

combination

 of IDH2

 of the cellular redox balance and,

 of IDH2 activity results in

Emodin anthraquinone),

*Rumex dentatus, R. abyssinicus,*

*bequaertii, R.* 

*zeylanica,Myrsine*

*Rapanea melanphloes,*

*Rheum palmatum*

*Rhamnus* 

*sphaerosperma*

 *Africana, Maesa lanceolata,*

 *Aloe saponaria*

*ruwenzoriensis,*

 *R. crispus; Plumbago*

 *R.* 

*usambarensis,*

 *R.*

(1,3,8-trihydroxy-6-methyl

NR assay.

A549

SPC212

DLD-1

Caco-2

MCF-7

HepG2

CRL2120.

Flow cytometric assay

Combination

treatment on cell cycle disturbance.

Cytomorphological

HaCaT

SiHa

C33A

HSC-3

Annexin-V

Caspase-3 Activity Emodin using 12.5–50 μg/mL

Western Blot DNA Damage Analysis

 Cell

 Viability

 of IDH2 knockdown

 and emodin

CYP-encoding

*DOI: http://dx.doi.org/10.5772/intechopen.95598*

**Ref.**

**microorganisms)**

*Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism DOI: http://dx.doi.org/10.5772/intechopen.95598*



**Quinona/ Natural origin (plants, animals,**

**35**

**Structure**

**Activity or model where it was tested**

MTT assay Annexin V/7-AAD

 **Results** IC50 μM A549 AGS MRC-5

(1) 11.3

(2) 3.0

(3) 45.3

(4) >50 > 50 > 50

(5) 46.6 27.4 28.7

None of the five compounds caspase-9 activity nor caspase-3.

 exert an effect upon

*DOI: http://dx.doi.org/10.5772/intechopen.95598*

*Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism*

 3.0

 1.7 1.7

 1.8 > 50

 8.7

**Ref.**

[36]

**microorganisms)**

Cyperaquinone

 (1) Hydroxycyperaquinone

Dihydrocyperaquinone

Tetrahydrocyperaquinone(4)

Scabequinone

*Cyperus spp.* Cleistopholine

MTT assay

IC50 μM

[37]

61.4

67.3

CAOV-3 cells showed evidenced by cell membrane blebbing, chromatin

compression

 and formation of apoptotic bodies.

morphological

 changes,

CAOV-3

SKOV-3

Assessment

acridine orange 86

double staining

 of apoptosis morphology

 using

(AO)/propidium

Annexin-V-FITC.

 iodide (PI)

*Enicosanthellum*

 *pulchrum*

 (5)

 (3)

 (2)

**Quinona/ Natural origin (plants, animals, microorganisms) Structure Activity or model where it was tested Results Ref.** Cyperaquinone (1) Hydroxycyperaquinone (2) Dihydrocyperaquinone (3) Tetrahydrocyperaquinone(4) Scabequinone (5) *Cyperus spp.* MTT assay Annexin V/7-AAD IC50 μM A549 AGS MRC-5 (1) 11.3 3.0 8.7 (2) 3.0 1.7 1.7 (3) 45.3 1.8 > 50 (4) >50 > 50 > 50 (5) 46.6 27.4 28.7 None of the five compounds exert an effect upon caspase-9 activity nor caspase-3. [36] Cleistopholine *Enicosanthellum pulchrum* MTT assay CAOV-3 SKOV-3 Assessment of apoptosis morphology using acridine orange 86 (AO)/propidium iodide (PI) double staining Annexin-V-FITC. IC50 μM 61.4 67.3 CAOV-3 cells showed morphological changes, evidenced by cell membrane blebbing, chromatin compression and formation of apoptotic bodies. [37]

### *Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism DOI: http://dx.doi.org/10.5772/intechopen.95598*


**Quinona/ Natural origin (plants, animals,**

**37**

**Structure**

**Activity or model where it was tested**

MTT assay

A549

SKMEL-28

V373

 **Results** IC50 μM.

3

2

3

**Ref.**

[41]

**microorganisms)**

2-methoxy-1,4-naphthoquinone

*Impatiens glandulifera* 5-methoxy-1,4-naphthoquinone

5,8-dihydroxy-1,4-naphthoquinone

2-hydroxy-1,4-naphthoquinone

2,5-dihydroxy-1,4-naphthoquinone

3,5-dihydroxy-1,4-naphthoquinone

3-methoxy juglone (6).

2-methoxy juglone (7).

3-ethoxy juglone (8).

2-ethoxy juglone (9).

Engelharquinone

*Juglans mandshurica*

 (10).

 (1).

MTT assay

IC50 μM

[25]

*DOI: http://dx.doi.org/10.5772/intechopen.95598*

(1) 68.72 (2) 16.11

(3) 18.83

(4) 15.37

*Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism*

(5) 7.33

(6) 43.54

(7) 22.38

(8) 30.42

(9) 32.51

(10) 34.80

HepG-2

 (2).

> (3).

 (4).

 (5).

*Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism DOI: http://dx.doi.org/10.5772/intechopen.95598*


**Quinona/ Natural origin (plants, animals,**

**39**

**Structure**

**Activity or model where it was tested**

MTT assay

Jurkat

HEK29

SH-SY5Y

 **Results** Cell viability %

62–95% at 50 μM

**Ref.**

[42]

**microorganisms)**

Knipholone

*Kniphofia foliosa* Hochst

β,β-dimethylacrylshikonin

MTT assay

IC50 μM

[19]

*DOI: http://dx.doi.org/10.5772/intechopen.95598*

*Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism*

24 h 48 h 72 h

18.7 11.6 4.30 14.7 7.88 4.13

MDA MB231 4 T1

*Lithospermum*

Mansonone-G

*Mansonia gagei*

 (MG).

SRB assay

IC50 μM

[43]

23

18.8

63.4

49.4

MCF

HeLa

HCT-116

HepG2

The resazurin reduction assay

IC50 μg/mL

[44]

0.16

0.28

0.58

0.89

0.27

0.61

0.27

0.26

0.22

>40

CCRF-CEM

CEM/ADR5000

MDA-MB231

MDAB231*/BCRP*

HCT116

*(p53+/+)*

HCT116*(p53/)*

U87MG

U87MG*.ΔEGFR*

HepG2

AML12

2-acetyl-7-methoxynaphtho[2,3-b]furan-4,9-

quinone

*Milletia versicolor*

*erythrorhizon*


## *Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism DOI: http://dx.doi.org/10.5772/intechopen.95598*


**Quinona/ Natural origin (plants, animals,**

**41**

**Structure**

**Activity or model where it was tested**

MTT cell viability assay

Cell cycle analysis

 **Results** IC50 μg/mL

72 h

MDA-MB-231

(1) 119

(2) 425

(3) 86

(4) 205

(5) 412

(6) 392

All compounds

cell lines. IC50 μg/mL

[49]

*Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism*

Weak activity

 induce cell cycle arrest in tumor

 HCT-116

 98 202

15

*DOI: http://dx.doi.org/10.5772/intechopen.95598*

301

 128 485

**Ref.**

[20]

**microorganisms)**

Deoxyshikonin

Isobutyrylshikonin

α-methylbutyrylshikonin

β5,8-

5,8-

*Onosma visianii* 1-hydroxy-6,8-dimethoxy-3-

MTT assay

Hela

HepG2

A549

methylanthracene-9,

8-hydroxy1,3-dimethoxy-6-

methylanthraquinone

xanthopurpurin

 (3). 2-methyl-1,3,6-trihydroxy-9,10-anthraquinone

(4).

*Osmunda japonica*

Physcion

MTT assay

IC50 μg/mL

[49]

[32]

Weak activity Showed higher cytotoxic effects

Induced apoptosis and necrosis

the caspase-3 activation pathway decreased the activation of AKT in all tumor cells, induction of reversible damage (DNA).

Changed the Levels of BAX and BCL-2

Inhibited AKT.

independent

 of

Hela,

HepG2

A549

Cytomorphological

HaCaT

SiHa

C33A

HSC-3

Annexin-V

Caspase-3 Activity Physcion using 12.5–50 μg/mL

Western Blot

DNA Damage Analysis

 Cell

 Viability

*Osmunda japonica*

*Rhamnus* 

*sphaerosperma*

 (2).

 10-dione (1).

*O*-dimethyl

deoxyshikonin

 (6).

*O*-dimethyl

isobutyrylshikonin

 (5).

hydroxyisovalerylshikonin

 (4).

 (3).

 (2).

 (1).


## *Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism DOI: http://dx.doi.org/10.5772/intechopen.95598*


**Quinona/ Natural origin (plants, animals,**

**43**

**Structure**

**Activity or model where it was tested**

Sulforhodamide

KKU-M156

Vero

Wound migration assay Chamber migration assay Chamber invasion assay. Gelatin

and uPA assay. Western blot analysis

Rhinacanthin

*Rhinacanthus*

 *nasutus*

 S

RM assay

IC50 μM

[52]

*Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism*

11.66

20

15.86

KB

MCF-7

NCI-H148

zymography

*DOI: http://dx.doi.org/10.5772/intechopen.95598*

 B assay

 **Results** IC50 μM

1.50

2.37

Inhibits the migration and invasion by decreasing

MMP-2, uPA, FAK and MAPK pathways

**Ref.**

[51]

**microorganisms)**

Rhinacanthin-C

*Rhinacanthus*

 *nasutus*


## *Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism DOI: http://dx.doi.org/10.5772/intechopen.95598*


**Quinona/ Natural origin (plants, animals,**

**45**

**Structure**

**Activity or model where it was tested**

SRB assay

 **Results** ED50 μM P-388

(1) 9.33

(2) >20

(3) 13.82 > 50 > 50

(4) >20

(5) >20

 37.31 38.81

> 50 > 50

*DOI: http://dx.doi.org/10.5772/intechopen.95598*

> 50 > 50

> 50 > 50

 KB Col-2

**Ref.**

[56]

**microorganisms)**

Ventilanone

Ventilanone

Ventilanone

Ventilanone

Ventilanone

*Ventilago*  **Marine sponge** Smenospongiarine

Smenospongorine

Smenospongimine

*Dactylospongia*

 *elegans*

 (3)

 (2)

 (1)

CCK-8 method

IC50 μM

[57]

*Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism*

ranging from 2.33 to 37.85

DU145

SW1990

Huh7 PANC-1

*harmandiana*

 E (5)

 D (4)

 C (3)

 B (2)

 A (1)

## *Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism DOI: http://dx.doi.org/10.5772/intechopen.95598*


**Quinona/ Natural origin (plants, animals,**

**47**

**Structure**

**Activity or model where it was tested**

WST-8 cell counting kit solution

A549

MCF-7

HeLa

 **Results** IC50 μM

8.9

5.9

8.6

**Ref.**

[60]

**microorganisms)**

Langcoquinones

The different genera *Dysidea*, *Spongia*, and

*Dactylospongia*

**Fugus**

Antrocinnamone

Quinone Q3 (2)

Antrocamol

 LT3 (3)

Antroquinonol

Antroquinonol

*Antrodia cinnamomea*

 B (5) 6,60-oxybis(1,3,8-trihydroxy-2-((S)-1-

MTT assay

IC50 μg/mL

[62]

values ranging from 11.25–17.36

SK-OV-3

SK-MEL-2

CNS

XF498

HCT-15

methoxyhexyl)anthracene-9,10-

6,60-oxybis(1,3,8-trihydroxy-2-((S)-1-

hydroxyhexyl)

10-O-methylaverantin

Averantin (4)

Averythrin

*Aspergillus versicolor*

 (5)

 (3).

anthracene9,10-dione)

 (2).

 dione) (1).

 (4)

 (1)

The cell counting kit-8 assay

IC50 μM

[61]

*DOI: http://dx.doi.org/10.5772/intechopen.95598*

MDCK A549 HepG2 PC3

(1) >100

(2) >100

(3) >100

(4) 10.53

(5) >100

 0.008 0.106 0.001

 0.421 0.044 0.073

 6.032 21.37 1.031

 0.382 > 100 0.014

 4.16 > 100 0.060

*Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism*

 D


## *Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism DOI: http://dx.doi.org/10.5772/intechopen.95598*

**Quinona/ Natural origin (plants, animals,**

**49**

**Structure**

**Activity or model where it was tested**

MTT assay

 **Results** IC50 μM MCF-7 A549 U87 PC3 (1) 12.39 > 40 9.01 14.59

(2) 25.0 > 40 13.45 19.93

**Ref.**

[66]

**microorganisms)**

Peniquinone

Peniquinone

*Penicillium* sp. L129

Altersolanol

*Phomopsis s*p.

(PM0409092)

 A

Monolayer assay propidium iodide (PI)

IC50 μg/mL

[67]

*DOI: http://dx.doi.org/10.5772/intechopen.95598*

*Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism*

0.001

0.001

0.001

0.001

0.287

0.001

0.052

0.004

0.027

0.001

0.004

0.001

0.412

0.01

0.001

0.001

0.034

0.001

0.001

0.001

0.006

0.013

0.049

0.001

0.012

BXF 1218 L

BXF T24 CNXF 498NL

CNXF SF268 CXF HCT116

CXF HT29 GXF 251 L

LXF 1121 L

LXF 289 L

LXF 526 L

LXF 529 L

LXF 629 L

LXF H460 MAXF 401NL

MAXF MCF7 MEXF 394NL MEXF 462NL

MEXF 514 L MEXF 520 L OVXF 1619 L

OVXF 899 L OVXFOVCAR

PAXF 1657 L PAXF PANC1

PRXF 22RV1

 B (2)

 A (1)


*Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism DOI: http://dx.doi.org/10.5772/intechopen.95598*


**Quinona/ Natural origin (plants, animals,**

**51**

**Structure**

**Activity or model where it was tested**

CCK-8 colorimetric

 method

 **Results** IC50 μg/ml HepG2 SF-268 ACHN

(1) 1.01

(2) 12.98

 3.04 10.08

 5.66 11.43

*DOI: http://dx.doi.org/10.5772/intechopen.95598*

**Ref.**

[70]

**microorganisms)**

51,4-dione (1). (S)-2,5-dihydroxy-2-methyl1,2,3,4-

tetrahydroanthracene-9,10-dione

*Micromonospora*

**Bacteria**

2-amino-6-hydroxy-[1,4]-benzoquinone

Detection of apoptosis for

fluorescence

 assay

 The percentage of apoptotic cancer cells (MGC-

803, HGC-27, 10 or 100 μM was significantly

MDA-MB-231,MDA-MB-435)

 increased

 at

[71]

*Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism*

*Geobacillus* sp. E263

Napyradiomycin

Napyradiomycin

Napyradiomycin

Napyradiomycin

*Streptomyces* sp. strain CA-271078

 SC (4)

 B7b (3)

 B7a (2)

 A3 (1)

MTT assay

IC50 μM

[72]

Values >50

HepG2

 sp. NEAU-gq13

 (2).

hydroxy-2-(2-hydroxypropyl)naphthalene-

## *Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism DOI: http://dx.doi.org/10.5772/intechopen.95598*

**Quinona/ Natural origin** 

**microorganisms)**

5-

1,4-dione (1). *Micromonospora*

**Bacteria**

*Geobacillus* sp. E263

Napyradiomycin

Napyradiomycin

Napyradiomycin

Napyradiomycin

*Streptomyces* sp. strain

 SC (4)

 B7b (3)

 B7a (2)

 A3 (1)

 sp.


*(EC50); Growth inhibition of 50% (IG50); Assay of* 

*(MHTBDE);*

*Resazurin microplate assay (RM); Crystal violet assay (CV).*

 *Cytotoxicity*

 *Assay for fluorescence*

 *(CAF); Neutral red uptake assay (NR);* 

*3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium*

 *bromide (MMT); Microscopy on a* 

*Sulforhodamine*

 *B assay (SRB); Trypan Blue Exclusion assay (TBE); Alamar Blue reduction assay (ABR);*

*hemocytometer*

 *using trypan blue dye exclusion method*

**Quinona/**

**animals, microorganisms)**

**Plants**

(*3*),

(*5*), 5,8-

5,8-

β -

Deoxyshikonin (

acetylshikonin (

*O*-dimethyl isobutyrylshikonin (

*O*-dimethyl deoxyshikonin (

*Onosma visianii*

Thymoquinone *Nigella sativa*

1,4,6-Trihydroxy-8 isoheptanyl-9,10 anthraquinone (symploquinone A) (1) 1,4-Dihydroxy-6-methyl-8-isopropyl-9,10 anthraquinone (symploquinone C) (2) *Symplocos racemosa*

Primin

**53**

*Miconia willdenowii*

isobutyrylshikonin (

α-methylbutyrylshikonin

hydroxyisovalerylshikonin

**Natural origin (plants,**

*1*),

*4*),

*7*).

*2*),

*DOI: http://dx.doi.org/10.5772/intechopen.95598*

*6*) and

**Structure Activity or model**

*Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism*

**where it was tested**

Micro-dilution antibacterial assay *B. megaterium E fecalis M. arborescens M. luteus S. epidermis C. Koseri H alvei P. proteolytica S. maltophilia Y. intermedia*

Broth microdilution volatilization method *Haemophilus influenzae Staphylococcus aureus Streptococcus pneumoniae*

Microdilution assay *S. aureus P mirabilis*

Mueller Hinton broth microdilution assay

*C. albicans ATCC*

*C. tropicalis ATCC*

*C. glabrata ATCC*

*10231 C. krusei ATCC*

*6258*

*750*

*90030 C. parapsilosis ATCC 22019 S. aureus (ATCC*

*6538)*

**Results Reference**

[20]

[47]

[76]

[77]

MIC 50 and 90 μg/

mL For all compounds Range: 8–51/ 9 – 54.28 6–34/6 –38

6 –34/6 –38

8 –68/9 –76

8 –51/9 –54

6 –68/6 –76

6 –51/6 –54

4 –68/6 –38

4 –68/4 –76

6 –25/6 –76

MIC (Broth/ agar) μg/

mL 8/8 16/16 16/32

MIC μg/mL (1) 160 (2) 83 (1) >160 (2) >160

IC50 μ M 72.08 36.04 72.08 72.08 72.08 8.94

**Quinona/ Natural origin (plants, animals, microorganisms) Structure Activity or model where it was tested Results Reference Plants** Deoxyshikonin (*1*), isobutyrylshikonin (*2*), α-methylbutyrylshikonin (*3*), acetylshikonin (*4*), βhydroxyisovalerylshikonin (*5*), 5,8-*O*-dimethyl isobutyrylshikonin (*6*) and 5,8-*O*-dimethyl deoxyshikonin (*7*). *Onosma visianii* Micro-dilution antibacterial assay *B. megaterium E fecalis M. arborescens M. luteus S. epidermis C. Koseri H alvei P. proteolytica S. maltophilia Y. intermedia* MIC 50 and 90 μg/ mL For all compounds Range: 8–51/ 9– 54.28 6–34/6–38 6–34/6–38 8–68/9–76 8–51/9–54 6–68/6–76 6–51/6–54 4–68/6–38 4–68/4–76 6–25/6–76 [20] Thymoquinone *Nigella sativa* Broth microdilution volatilization method *Haemophilus influenzae Staphylococcus aureus Streptococcus pneumoniae* MIC (Broth/ agar) μg/ mL 8/8 16/16 16/32 [47] 1,4,6-Trihydroxy-8 isoheptanyl-9,10 anthraquinone (symploquinone A) (1) 1,4-Dihydroxy-6-methyl-8-isopropyl-9,10 anthraquinone (symploquinone C) (2) *Symplocos racemosa* Microdilution assay *S. aureus P mirabilis* MIC μg/mL (1) 160 (2) 83 (1) >160 (2) >160 [76] Primin *Miconia willdenowii* Mueller Hinton broth microdilution assay *C. albicans ATCC 10231 C. krusei ATCC 6258 C. tropicalis ATCC 750 C. glabrata ATCC 90030 C. parapsilosis ATCC 22019 S. aureus (ATCC 6538)* IC50 μM 72.08 36.04 72.08 72.08 72.08 8.94 [77]

*Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism DOI: http://dx.doi.org/10.5772/intechopen.95598*


compound to obtain the results. There are different methods to carry out these tests. In this review, the activities were determined by the use of MTT, SRB, NR, IDO,

**Structure Activity or model**

*Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism*

**where it was tested**

Microdilution assay Methicillinresistant Staphylococcus aureus MB5393; *Mycobacterium tuberculosis* H37Ra

Microdilution assay *S. aureus M. tuberculosis* **Results Reference**

[72]

MIC μg/mL Values ranging 3– 48

MIC μg/mL (1) 4 (2) 6 (1) > 160 (2) 4

[81]

Quinones have good activity against numerous cell cancer lines; they also exhibit good antimicrobial activity. This situation, along with the wide variety of structures that these compounds exhibit, make them a very interesting topic to continue to explore for other mechanisms of action and the chemical modification of their

sulforhodamine B, AGS, Trypan blue, immunophenotyping, Alamar blue, FITC Annexin V Apoptosis, the CCK-8 colorimetric method, and Annexin V/7-AAD. The determination of antimicrobial activity was carried out by MIC,

iodide propidium, violet crystal, cell counting kits, resazurin reduction,

micro-dilution, and broth microdilution volatilization.

The authors declare no conflict of interest.

structures, among other topics.

*Minimum inhibitory concentration (MIC).*

*Quinones with antimicrobial activity.*

**Conflict of interest**

**55**

**Quinona/**

**animals, microorganisms)**

**Bacteria**

271078

Animal

*melici*

**Table 2.**

3,5- dimethoxy-2- (methylthio)cyclohexa-2,5-diene-1,4-dione (1) 5-methoxy-2,3- bis (methylthio)cyclohexa-2,5-diene-1,4-dione (2) Venom of *Diplocentrus*

**Natural origin (plants,**

*DOI: http://dx.doi.org/10.5772/intechopen.95598*

Napyradiomycin A (1) Napyradiomycin B (2) napyradiomycin SC (3) napyradiomycin D1 (4) *Streptomyces* sp. strain CA- *Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism DOI: http://dx.doi.org/10.5772/intechopen.95598*

#### **Table 2.**

*Quinones with antimicrobial activity.*

compound to obtain the results. There are different methods to carry out these tests. In this review, the activities were determined by the use of MTT, SRB, NR, IDO, iodide propidium, violet crystal, cell counting kits, resazurin reduction, sulforhodamine B, AGS, Trypan blue, immunophenotyping, Alamar blue, FITC Annexin V Apoptosis, the CCK-8 colorimetric method, and Annexin V/7-AAD.

The determination of antimicrobial activity was carried out by MIC, micro-dilution, and broth microdilution volatilization.

Quinones have good activity against numerous cell cancer lines; they also exhibit good antimicrobial activity. This situation, along with the wide variety of structures that these compounds exhibit, make them a very interesting topic to continue to explore for other mechanisms of action and the chemical modification of their structures, among other topics.

## **Conflict of interest**

The authors declare no conflict of interest.

*Cytotoxicity - New Insights into Toxic Assessment*

## **Author details**

Nimsi Campos-Xolalpa<sup>1</sup> , Julia Pérez-Ramos<sup>1</sup> , Ana Esquivel-Campos<sup>1</sup> , Cuauhtemoc Pérez-González<sup>1</sup> , Leonor Sánchez-Pérez<sup>2</sup> and Salud Pérez-Gutiérrez<sup>1</sup> \* **References**

md17090491.

fct.2019.04.012.

[1] Khalifa SAM, Elias N, Farag MA, Chen L, Saeed A, Hegazy MF, Moustafa MS, Abd El-Washed A, Al- Mousawi SM, Musharraf SG, Chang FR, Iwasaku A, Suenaga K, Alajlani M, Göransson U, El-Seedi HR. Marine Natural products: A source of novel anticancer drugs. Mar Drugs. 2019;17:491-522. DOI: 10.3390/

*DOI: http://dx.doi.org/10.5772/intechopen.95598*

*Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism*

[8] Borchardt JK. The beginnings of drugs therapy: ancient Mesopotamian medicine. Drug News Perspect. 2002;15:

[9] Saha S, Sadhukhan P, Sil P. Genistein: a phytoestrogen with multifaceted therapeutic properties. Mini Rev Med Chem. 2014;14:920-940. DOI: 10.2174/

187-192. DOI: 10.1358/ dnp.2002.15.3.840015.

1389557514666141029233442.

H, Lee YS, Riaz N, Jabbar A. Antimicrobial natural products: an update on future antibiotic drug candidates. Nat Prod Rep. 2010;27: 238-254. DOI: 10.1039/b916096e.

[10] Asche C. Antitumour quinones. Mini Rev Med Chem. 2005;5:449-467. DOI: 10.2174/1389557053765556.

[11] Saleem M, Nazir M, Ali MS, Hussain

[12] Hong-Ru W, Wei Z, Xiao-Yan P, Yuan G, Xian MU. Obulqasim, Hong-

[13] Li Y, Dong C, Xu MJ, Lin WH. New

mangrove plant Aegiceras Corniculatum with anticancer activity. J Asian Nat Prod Res. 2020;22:121-130. DOI: 10.1080/10286020.2018.1540604.

[15] Asaumi S, Kawakami S, Sugimoto S, Matsunami K, Otsuka H, Shinzato T.

ardisiaquinones A–H from the leaves of Ardisia quinquegona and their antileishmania activity. Chem Pharm Bull.

Fang L, Ying Z. Quinones and coumarins from Ajania salicifolia and their radical scavenging and cytotoxic activity. J Asian Nat Prod Res. 2015;17:

1196-1203. DOI: 10.1080/ 10286020.2015.1117456

alkylated benzoquinones from

[14] Abdissa N, Gohlk, S, Frese M, Sewald N. Cytotoxic compounds from aloe megalacantha. Molecules. 2017;22:

1136-1141. DOI:10.3390/ molecules22071136.

Alkylated benzoquinones:

[2] Dutta S, Mahalanobish S, Saha S, Ghosh S, Sil PC. Natural products: An uncoming therapeutic approach to cancer. Food Chem Toxicol. 2019;

[3] Gallagher EJ, Neel BA, Antoniou IM, Yakar S, LeRoith D. The increased risk of cancer in obesity and type 2 diabetes: potential mechanisms. In: Poretsky, L. Editor. Principle of Diabetes mellitus. Springer International Publishing, Cham; 2017. 731-753 pp. DOI: 10.1007/

[4] White MC, Holman DM, Boehm JE, Peipins LA, Grossman M, Henley SJ. Age and cancer risk. A potential modificable relationship. Am J Prev Med. 2014;46:S7-S15. DOI: 10.1016/j.

[5] Prestinaci F, Pezzotti P, Pantosti A. Antimicrobial resistance: A global multifaceted phenomenon. Pathog Glob Health. 2015;109:309–318. DOI: 10.1179/

128:240-255. DOI: 10.1016/j.

978-0-387-09841-8\_36).

amepre.2013.10.029.

2047773215Y.0000000030.

[6] Morehead MS, Scarbrough C. Emergence of global antibiotic

resistance. Prim Care. 2018;45:467-484. DOI: 10.1016/j.pop.2018.05.006.

[7] Morgan D, Okeke R, Laxminarayan R, Perencevich E, Weisenberg S. Non-prescription antimicrobial use worldwide: A systematic review.

Lancet Infect Dis. 2011;11:692-701. DOI: 10.1016/S1473-3099(11)70054-8.

**57**

1 Department of Biological Systems, Universidad Autónoma Metropolitana-Xochimilco, Calzada del Hueso 1100, Col. Villa Quietud Ciudad de México, México

2 Department of Health Attention, Universidad Autónoma Metropolitana-Xochimilco, Calzada del Hueso 1100, Col. Villa Quietud Ciudad de México, México

\*Address all correspondence to: msperez@correo.xoc.uam.mx

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism DOI: http://dx.doi.org/10.5772/intechopen.95598*

## **References**

[1] Khalifa SAM, Elias N, Farag MA, Chen L, Saeed A, Hegazy MF, Moustafa MS, Abd El-Washed A, Al- Mousawi SM, Musharraf SG, Chang FR, Iwasaku A, Suenaga K, Alajlani M, Göransson U, El-Seedi HR. Marine Natural products: A source of novel anticancer drugs. Mar Drugs. 2019;17:491-522. DOI: 10.3390/ md17090491.

[2] Dutta S, Mahalanobish S, Saha S, Ghosh S, Sil PC. Natural products: An uncoming therapeutic approach to cancer. Food Chem Toxicol. 2019; 128:240-255. DOI: 10.1016/j. fct.2019.04.012.

[3] Gallagher EJ, Neel BA, Antoniou IM, Yakar S, LeRoith D. The increased risk of cancer in obesity and type 2 diabetes: potential mechanisms. In: Poretsky, L. Editor. Principle of Diabetes mellitus. Springer International Publishing, Cham; 2017. 731-753 pp. DOI: 10.1007/ 978-0-387-09841-8\_36).

[4] White MC, Holman DM, Boehm JE, Peipins LA, Grossman M, Henley SJ. Age and cancer risk. A potential modificable relationship. Am J Prev Med. 2014;46:S7-S15. DOI: 10.1016/j. amepre.2013.10.029.

[5] Prestinaci F, Pezzotti P, Pantosti A. Antimicrobial resistance: A global multifaceted phenomenon. Pathog Glob Health. 2015;109:309–318. DOI: 10.1179/ 2047773215Y.0000000030.

[6] Morehead MS, Scarbrough C. Emergence of global antibiotic resistance. Prim Care. 2018;45:467-484. DOI: 10.1016/j.pop.2018.05.006.

[7] Morgan D, Okeke R, Laxminarayan R, Perencevich E, Weisenberg S. Non-prescription antimicrobial use worldwide: A systematic review. Lancet Infect Dis. 2011;11:692-701. DOI: 10.1016/S1473-3099(11)70054-8.

[8] Borchardt JK. The beginnings of drugs therapy: ancient Mesopotamian medicine. Drug News Perspect. 2002;15: 187-192. DOI: 10.1358/ dnp.2002.15.3.840015.

[9] Saha S, Sadhukhan P, Sil P. Genistein: a phytoestrogen with multifaceted therapeutic properties. Mini Rev Med Chem. 2014;14:920-940. DOI: 10.2174/ 1389557514666141029233442.

[10] Asche C. Antitumour quinones. Mini Rev Med Chem. 2005;5:449-467. DOI: 10.2174/1389557053765556.

[11] Saleem M, Nazir M, Ali MS, Hussain H, Lee YS, Riaz N, Jabbar A. Antimicrobial natural products: an update on future antibiotic drug candidates. Nat Prod Rep. 2010;27: 238-254. DOI: 10.1039/b916096e.

[12] Hong-Ru W, Wei Z, Xiao-Yan P, Yuan G, Xian MU. Obulqasim, Hong-Fang L, Ying Z. Quinones and coumarins from Ajania salicifolia and their radical scavenging and cytotoxic activity. J Asian Nat Prod Res. 2015;17: 1196-1203. DOI: 10.1080/ 10286020.2015.1117456

[13] Li Y, Dong C, Xu MJ, Lin WH. New alkylated benzoquinones from mangrove plant Aegiceras Corniculatum with anticancer activity. J Asian Nat Prod Res. 2020;22:121-130. DOI: 10.1080/10286020.2018.1540604.

[14] Abdissa N, Gohlk, S, Frese M, Sewald N. Cytotoxic compounds from aloe megalacantha. Molecules. 2017;22: 1136-1141. DOI:10.3390/ molecules22071136.

[15] Asaumi S, Kawakami S, Sugimoto S, Matsunami K, Otsuka H, Shinzato T. Alkylated benzoquinones: ardisiaquinones A–H from the leaves of Ardisia quinquegona and their antileishmania activity. Chem Pharm Bull.

2018;66:757-763. DOI: 10.1248/cpb. c18-00281.

[16] Yuzbasioglu Baran M, Guvenalp Z, Saracoglu I, Kazaz C, Salih B, Demirezer LO, Kuruuzum-Uz A. Cytotoxic naphthoquinones from Arnebia densiflora (Nordm.) Ledeb and determining new apoptosis inducers. Nat Prod Res. 2020;34:1669-1677. DOI: 10.1080/14786419.2018.1525714.

[17] Byeon SE, Yi YS, Lee J, Yang WS, Kim JH, Kim J, Hong S, Cho JY. Hydroquinone exhibits in vitro and in vivo anti-cancer activity in cancer cells and mice. Int J Mol Sci. 2018;19: 903-916. DOI: 10.3390/ijms19030903.

[18] Park SH, Phuc NM, Lee J, Wu Z, Kim J, Kim H, Kim ND, Lee T, Song KS, Liu KH. Identification of acetylshikonin as the novel CYP2J2 inhibitor with anticancer activity in HepG2 cells. Phytomedicine. 2017;15;24:134-140. DOI: 10.1016/j.phymed.2016.12.001.

[19] Chen Y, Chen ZY, Chen L, Zhang JY, Fu LY, Tao L, Zhang Y, Hu XX, Shen XC. Shikonin inhibits triple-negative breast cancer-cell metastasis by reversing the epithelial-to-mesenchymal transition via glycogen synthase kinase 3β-regulated suppression of β-catenin signaling. Biochem Pharmacol. 2019; 166:33-45. DOI: 10.1016/j. bcp.2019.05.001.

[20] Vukic MD, Vukovic NL, Djelic GT, Popovic SL, Zaric MM, Baskic DD, Krstic GB, Tesevic VV, Kacaniova MM. Antibacterial and cytotoxic activities of naphthoquinone pigments from Onosma visianii Clem. Excli J. 2017;16: 73-88. DOI: 10.17179/excli2016-762.

[21] Trivedi R, Müller GA, Rathore MS, Mishra DP, Dihazi H. Anti-leukemic activity of Shikonin: role of ERP57 in Shikonin induced apoptosis in acute myeloid leukemia. Cell Physiol Biochem. 2016;39:604-16. DOI: 10.1159/ 000445652.

[22] Spyrelli ED, Kyriazou AV, Virgiliou C, Nakas A, Deda O, Papageorgiou VP, Assimopoulou AN, Gika HG. Metabolic profiling study of shikonin's cytotoxic activity in the Huh7 human hepatoma cell line. Mol Biosyst. 2017;13:841-851. DOI: 10.1039/C6MB00830E.

instability of human breast cancer cells. Biomed. Pharmacother. 2016;82:

*DOI: http://dx.doi.org/10.5772/intechopen.95598*

*Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism*

exerts potent anticancer effects in MIAPaCa-2 and PANC-1 human pancreatic adenocarcinoma cell lines through activation of both apoptotic and autophagic pathways, sub-G1 cell cycle arrest and disruption of mitochondrial membrane potential (ΛΨm). J BUON. 2019;24:746-753. PMID: 31128032.

[35] Zhou M, Xing HH, Yang Y, Wang YD, Zhou K, Dong W, W, Li GP, Hu WY, Liu Q, Li XM, Hu QF. Three new anthraquinones from the twigs of Cassia fistula and their bioactivities. J Asian Nat Prod Res. 2017;19:1073-1078. DOI: 10.1080/10286020.2017.1285911.

[36] Ribeiro V, Andrade PB, Valentão P, Pereira DM. Benzoquinones from Cyperus spp. trigger IRE1α-independent and PERK-dependent ER stress in human stomach cancer cells and are

Phytomedicine. 2019;63:153017. DOI: 10.1016/j.phymed.2019.153017.

[37] Nordin N, Majid NA, Mohan S, Dehghan F, Karimian H, Rahman MA, Ali HM, Hashim NM. Cleistopholine isolated from Enicosanthellum pulchrum exhibits apoptogenic properties in human ovarian cancer cells. Phytomedicine. 2016;23:406-416. DOI: 10.1016/j.phymed.2016.02.016.

[38] Bigolin A, Maioral MF, Stefanes NM, Zatelli GA, Philippus AC, Falkenberg MB, Santos-Silva MC. Cytotoxic mechanisms of primin, a natural quinone isolated from Eugenia hiemalis, on hematological cancer cell lines. Anticancer Drugs. 2020;31:

[39] Thanuphol P, Asami Y, Shiomi K. Wongnoppavich A, Tuchinda P, Soonthornchareonnon N. Marcanine G, a new cytotoxic 1-azaanthraquinone from the stem bark of Goniothalamus marcanii Craib. Nat Prod Res. 2018;32:

709-717. DOI: 10.1097/ CAD.0000000000000937.

1682-1689. DOI: 10.1080/ 14786419.2017.1396588.

novel proteasome inhibitors.

[29] Kuete V, Omosa LK, Tala VR, Midiwo JO, Mbaveng AT, Swaleh S, Karaosmanoğlu O, Sivas H. Cytotoxicity of Plumbagin, Rapanone and 12 other naturally occurring Quinones from Kenyan Flora towards human carcinoma cells. BMC Pharmacol Toxico. 2016;17:1-10. DOI: 10.1186/

[30] Mancilla IA, Coatti GC, Biazi BI, Zanetti TA, Baranoski A, Marques LA, Corveloni AC, Lepri SR, Mantovani MS. Molecular pathways related to the control of proliferation and cell death in 786-O cells treated with plumbagin. Mol Biol Rep. 2019;46:6071-6078. DOI: 10.1007/s11033-019-05042-9.

[31] Ku HJ, Kwon OS, Kang BS, Lee DS, Lee HS, Park JW. IDH2 knockdown sensitizes tumor cells to Emodin cytotoxicity in vitro and in vivo. Free Radic Res. 2016;50:1089-1097. DOI: 10.1080/10715762.2016.1178739.

[32] Moreira TF, Sorbo JM, Souza FDO, Fernandes BC, Ocampos FMM, de Oliveira DMS, Arcaro CA, Assis RP, Barison A, Miguel OG, Baviera AM, Soares CP, Brunetti IL. Emodin, Physcion, and crude extract of Rhamnus sphaerosperma var. pubescens induce mixed cell death, increase in oxidative stress, DNA damage, and inhibition of AKT in cervical and Oral squamous carcinoma cell lines. Oxid Med Cell Longev. 2018;2018:1-18. DOI: 10.1155/

[33] Li R, Li W, You Y, Guo X, Peng Y, Zheng J. Metabolic activation and cytotoxicity of Aloe-Emodin mediated by sulfotransferases. Chem Res Toxicol. 2019;32:1281-1288. DOI: 10.1021/acs.

[34] Du Y, Zhang J, Tao Z, Wang C, Yan S, Zhang X, Huang M. Aloe emodin

2018/2390234.

chemrestox.9b00081.

**59**

256-268. DOI: 10.1016/j. biopha.2016.05.007.

s40360-016-0104-7.

[23] Pavan V, Ribaudo G, Zorzan M, Redaelli M, Pezzani R, Mucignat-Caretta C, Zagotto G. Antiproliferative activity of Juglone derivatives on rat glioma. Nat Prod Res. 2017;31:632-638. DOI: 10.1080/14786419.2016.1214830.

[24] Zhou YY, Guo S, Wang Y, Song HJ, Gao HR, Zhang XJ, Sun YP, Liu Y, Yang BY, Kuang HX. α-Tetralone glycosides from the green walnut husks of Juglans mandshurica Maxim. and their cytotoxic activities. Nat Prod Res. 2020; 34:1805-1813. DOI: 10.1080/ 14786419.2018.1561681.

[25] Zhou Y, Yang B, Jiang Y, Liu Z, Liu Y, Wang X, Kuang H. Studies on cytotoxic activity against HepG-2 cells of naphthoquinones from green walnut husks of Juglans mandshurica Maxim. Molecules. 2015;20:15572-15588. DOI: 10.3390/molecules200915572.

[26] Wu J, Zhang H, Xu Y, Zhang J, Zhu W, Zhang Y, Chen L, Hua W, Mao Y. Juglone induces apoptosis of tumor stem-like cells through ROS-p38 pathway in glioblastoma. BMC Neurology. 2017;17:70-76. DOI: 10.1186/ s12883-017-0843-0.

[27] De U, Son JY, Jeon Y, Ha SY, Park YJ, Yoon S, Ha KT, Choi WS, Lee BM, Kim IS, Kwak JH, Kim HS. Plumbagin from a tropical pitcher plant (Nepenthes alata Blanco) induces apoptotic cell death via a p53-dependent pathway in MCF-7 human breast cancer cells. Food Chem Toxicol. 2019;123:492-500. DOI: 10.1016/j.fct.2018.11.040.

[28] Sameni S, Hande MP. Plumbagin triggers DNA damage response, telomere dysfunction and genome

*Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism DOI: http://dx.doi.org/10.5772/intechopen.95598*

instability of human breast cancer cells. Biomed. Pharmacother. 2016;82: 256-268. DOI: 10.1016/j. biopha.2016.05.007.

[29] Kuete V, Omosa LK, Tala VR, Midiwo JO, Mbaveng AT, Swaleh S, Karaosmanoğlu O, Sivas H. Cytotoxicity of Plumbagin, Rapanone and 12 other naturally occurring Quinones from Kenyan Flora towards human carcinoma cells. BMC Pharmacol Toxico. 2016;17:1-10. DOI: 10.1186/ s40360-016-0104-7.

[30] Mancilla IA, Coatti GC, Biazi BI, Zanetti TA, Baranoski A, Marques LA, Corveloni AC, Lepri SR, Mantovani MS. Molecular pathways related to the control of proliferation and cell death in 786-O cells treated with plumbagin. Mol Biol Rep. 2019;46:6071-6078. DOI: 10.1007/s11033-019-05042-9.

[31] Ku HJ, Kwon OS, Kang BS, Lee DS, Lee HS, Park JW. IDH2 knockdown sensitizes tumor cells to Emodin cytotoxicity in vitro and in vivo. Free Radic Res. 2016;50:1089-1097. DOI: 10.1080/10715762.2016.1178739.

[32] Moreira TF, Sorbo JM, Souza FDO, Fernandes BC, Ocampos FMM, de Oliveira DMS, Arcaro CA, Assis RP, Barison A, Miguel OG, Baviera AM, Soares CP, Brunetti IL. Emodin, Physcion, and crude extract of Rhamnus sphaerosperma var. pubescens induce mixed cell death, increase in oxidative stress, DNA damage, and inhibition of AKT in cervical and Oral squamous carcinoma cell lines. Oxid Med Cell Longev. 2018;2018:1-18. DOI: 10.1155/ 2018/2390234.

[33] Li R, Li W, You Y, Guo X, Peng Y, Zheng J. Metabolic activation and cytotoxicity of Aloe-Emodin mediated by sulfotransferases. Chem Res Toxicol. 2019;32:1281-1288. DOI: 10.1021/acs. chemrestox.9b00081.

[34] Du Y, Zhang J, Tao Z, Wang C, Yan S, Zhang X, Huang M. Aloe emodin

exerts potent anticancer effects in MIAPaCa-2 and PANC-1 human pancreatic adenocarcinoma cell lines through activation of both apoptotic and autophagic pathways, sub-G1 cell cycle arrest and disruption of mitochondrial membrane potential (ΛΨm). J BUON. 2019;24:746-753. PMID: 31128032.

[35] Zhou M, Xing HH, Yang Y, Wang YD, Zhou K, Dong W, W, Li GP, Hu WY, Liu Q, Li XM, Hu QF. Three new anthraquinones from the twigs of Cassia fistula and their bioactivities. J Asian Nat Prod Res. 2017;19:1073-1078. DOI: 10.1080/10286020.2017.1285911.

[36] Ribeiro V, Andrade PB, Valentão P, Pereira DM. Benzoquinones from Cyperus spp. trigger IRE1α-independent and PERK-dependent ER stress in human stomach cancer cells and are novel proteasome inhibitors. Phytomedicine. 2019;63:153017. DOI: 10.1016/j.phymed.2019.153017.

[37] Nordin N, Majid NA, Mohan S, Dehghan F, Karimian H, Rahman MA, Ali HM, Hashim NM. Cleistopholine isolated from Enicosanthellum pulchrum exhibits apoptogenic properties in human ovarian cancer cells. Phytomedicine. 2016;23:406-416. DOI: 10.1016/j.phymed.2016.02.016.

[38] Bigolin A, Maioral MF, Stefanes NM, Zatelli GA, Philippus AC, Falkenberg MB, Santos-Silva MC. Cytotoxic mechanisms of primin, a natural quinone isolated from Eugenia hiemalis, on hematological cancer cell lines. Anticancer Drugs. 2020;31: 709-717. DOI: 10.1097/ CAD.0000000000000937.

[39] Thanuphol P, Asami Y, Shiomi K. Wongnoppavich A, Tuchinda P, Soonthornchareonnon N. Marcanine G, a new cytotoxic 1-azaanthraquinone from the stem bark of Goniothalamus marcanii Craib. Nat Prod Res. 2018;32: 1682-1689. DOI: 10.1080/ 14786419.2017.1396588.

[40] Zhu H, Zheng Z, Zhang J, Liu X, Liu Y, Yang W, Liu Y, Zhang T, Zhao Y, Liu Y, Su X, Gu X. Anticancer effect of 2,7 dihydroxy-3-methylanthraquinone on human gastric cancer SGC-7901 cells in vitro and in vivo. Pharm Biol. 2016; 54:285-92. DOI: 10.3109/ 13880209.2015.1033563.

[41] Cimmino A, Mathieu V, Evidente M, Ferderin M, Moreno Y, Banuls L, Masi M, De Carvalho A, Kiss R, Evidente A. Glanduliferins A and B, two new glucosylated steroids from Impatiens glandulifera, with in vitro growth inhibitory activity in human cancer cells. Fitoterapia. 2016;109: 138-45. DOI: 0.1016/j.fitote.2015.12.016.

[42] Feilcke R, Arnouk G, Raphane B, Richard K, Tietjen I, Andrae-Marobela K, Erdmann F, Schipper S, Becker K, Arnold N, Frolov A, Reiling N, Imming P, Fobofou SAT. Biological activity and stability analyses of knipholone anthrone, a phenyl anthraquinone derivative isolated from Kniphofia foliosa Hochst. J Pharm Biomed Anal. 2019;174:277-285. DOI: 10.1016/j. jpba.2019.05.065.

[43] Baghdadi MA, Al-Abbasi FA, El-Halawany AM, Aseeri AH, Al-Abd AM. Anticancer profiling for coumarins and related O-naphthoquinones from Mansonia gagei against solid tumor cells in vitro. Molecules. 2018;23:1020-1033. DOI: 10.3390/molecules23051020.

[44] Kuete V, Mbaveng AT, Sandjo LP, Zeino M, Efferth T. Cytotoxicity and mode of action of a naturally occurring naphthoquinone, 2-acetyl-7 methoxynaphtho [2, 3-b] furan-4, 9 quinone towards multi-factorial drugresistant cancer cells. Phytomedicine. 2017;33:62-68. DOI: 10.1016/j. phymed.2017.07.010.

[45] Abu N, Zamberi NR, Yeap SK, Nordin N, Mohamad NE, Romli MF, Rasol NE, Subramani T, Ismail NH, Alitheen NB. Subchronic toxicity,

immunoregulation and anti-breast tumor effect of Nordamnacantal, an anthraquinone extracted from the stems of Morinda citrifolia L. BMC Complem Altern M. 2018;18:18-31. DOI: 10.1186/ s12906-018-2102-3.

invasion by decreasing MMP-2, uPA, FAK and MAPK pathways. Asian Pac J Cancer Prev. 2018;19:3605-3613. DOI: 10.31557/APJCP.2018.19.12.3605.

*DOI: http://dx.doi.org/10.5772/intechopen.95598*

*Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism*

[57] Yu HB, Yin ZF, Gu BB, Zhang JP, Wang SP, Yang F, Lin HW. Cytotoxic meroterpenoids from the marine sponge Dactylospongia elegans. Nat Prod Res.

[58] Neupane RP, Parrish SM, Neupane J, Yoshida WY, Yip ML, Turkson J, Harper MK, Head JD, Williams PG. Cytotoxic sesquiterpenoid quinones and

2019:1-7. DOI: 10.1080/ 14786419.2019.1633644.

quinols, and an 11-membered heterocycle, Kauamide, from the

Dactylospongia elegans. Mar Drugs. 2019;17:423-428. DOI: 10.3390/

[59] Luo X, Li P, Wang K, de Voogd NJ, Tang X, Li G. Cytotoxic sesquiterpenoid quinones from South China Sea sponge Dysidea sp. Nat Prod Res. 2019;1-6. DOI: 10.1080/14786419.2019.1679132.

[60] Ito T, Nguyen HM, Win NN, Vo HQ, Nguyen HT, Morita H. Three new sesquiterpene aminoquinones from a Vietnamese Spongia sp. and their biological activities. J Nat Med. 2018;72: 298–303. DOI: 10.1007/s11418-017-

[61] Yen I, Lee SY, Lin KT, Lai FY, Kuo MT, Chang WL. In vitro anticancer activity and structural characterization

[62] Li JL, Jiang X, Liu X, He C, Di Y, Lu S, Huang H, Lin B, Wang D, Fan B. Antibacterial anthraquinone dimers from marine derived fungus Aspergillus sp. Fitoterapia. 2019;133:1-4. DOI: 10.1016/j.fitote.2018.11.015.

[63] Wang M, Sun ZH, Chen YC, Liu HX, Li HH, Tan GH, Li SN, Guo XL, Zhang W. Cytotoxic cochlioquinone derivatives from the endophytic fungus Bipolaris sorokiniana derived from Pogostemon cablin. Fitoterapia. 2016;

of ubiquinones from Antrodia cinnamomea mycelium. Molecules. 2017;22:747-752. DOI: 10.3390/

molecules22050747.

Hawaiian marine sponge

md17070423.

1130-5.

[52] Boonyaketgoson S, Rukachaisirikul

[53] Dias RB, de Araújo TBS, de Freitas RD, Rodrigues ACBDC, Sousa LP, Sales CBS, Valverde LF, Soares MBP, Dos Reis MG, Coletta RD, Ramos EAG, Camara CA, Silva TMS, Filho JMB, Bezerra DP, Rocha CAG. β-Lapachone and its iodine derivatives cause cell cycle arrest at G2/M phase and reactive oxygen species-mediated apoptosis in human oral squamous cell carcinoma cells. Free Radic Biol Med. 2018;126:87-100. DOI: 10.1016/j.freeradbiomed.2018.

[54] Zada S, Hwang JS, Ahmed M, Lai TH, Pham TM, Kim DH, Kim DR. Protein kinase A activation by β Lapachone is associated with apoptotic cell death in NQO1 overexpressing breast cancer cells. Oncol Rep. 2019;42: 1621-1630. DOI: 10.3892/or.2019.7243.

[55] Zhang Q, Chen L, Hu LJ, Liu WY,

rhynchophylla. Chin J Nat Med. 2016; 14:232-235. DOI: 10.1016/S1875-5364

Kuhakarn C, Piyachaturawat P, Suksen K, Panthong A, Chiranthanut N, Kongsaeree P, Prabpai S, Nuntasaen N, Reutrakul V. Pyranonaphthoquinone and anthraquinone derivatives from Ventilago harmandiana and their potent

Phytochemistry. 2020;169:112182. DOI: 10.1016/j.phytochem.2019.112182.

Feng F, Qu W. Two new ortho benzoquinones from Uncaria

[56] Panthong K, Hongthong S,

anti-inflammatory activity.

(16)30021-8.

**61**

V, Phongpaichit S, Trisuwan K. Naphthoquinones from the leaves of Rhinacanthus nasutus having acetylcholinesterase inhibitory and cytotoxic activities. Fitoterapia. 2018;

124: 206-210 DOI: 10.1016/j.

fitote.2017.11.011

07.022.

[46] Alobaedi OH, Talib WH, Basheti IA. Antitumor effect of thymoquinone combined with resveratrol on mice transplanted with breast cancer. Asian Pac J Trop Med. 2017;10:400-408. DOI: 10.1016/j.apjtm.2017.03.026.

[47] Houdkova M, Rondevaldova J, Doskocil I, Kokoska L. Evaluation of antibacterial potential and toxicity of plant volatile compounds using new broth microdilution volatilization method and modified MTT assay. Fitoterapia. 2017;118:56-62. DOI: 10.1016/j.fitote.2017.02.008.

[48] Arumugam P, Subramanian R, Priyadharsini JV, Gopalswamy J. Thymoquinone inhibits the migration of mouse neuroblastoma (Neuro-2a) cells by down-regulating MMP-2 and MMP-9. Chin J Nat Med. 2016;14:904-912. DOI: 10.1016/S1875-5364(17)30015-8.

[49] Bowen L, Li C, Bin L, Ying T, Shijun L, Junxing D. Chemical constituents, cytotoxic and antioxidant activities of extract from the rhizomes of Osmunda japonica Thunb. Nat Prod Res. 2020;34: 847-850. DOI: 10.1080/ 14786419.2018.1501692.

[50] Bajpai VK, Alam MB, Quan KT, Choi HJ, An H, Ju MK, Lee SH, Huh YS, Han YK, Na M. Cytotoxic properties of the anthraquinone derivatives isolated from the roots of Rubia philippinensis. BMC Complem Altern Med. 2018;18: 200-206. DOI: 10.1186/s12906-018- 2253-2.

[51] Boueroy P, Saensa-Ard S, Siripong P, Kanthawong S, Hahnvajanawong C. Rhinacanthin-C extracted from Rhinacanthus nasutus (L.) inhibits cholangiocarcinoma cell migration and *Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism DOI: http://dx.doi.org/10.5772/intechopen.95598*

invasion by decreasing MMP-2, uPA, FAK and MAPK pathways. Asian Pac J Cancer Prev. 2018;19:3605-3613. DOI: 10.31557/APJCP.2018.19.12.3605.

[52] Boonyaketgoson S, Rukachaisirikul V, Phongpaichit S, Trisuwan K. Naphthoquinones from the leaves of Rhinacanthus nasutus having acetylcholinesterase inhibitory and cytotoxic activities. Fitoterapia. 2018; 124: 206-210 DOI: 10.1016/j. fitote.2017.11.011

[53] Dias RB, de Araújo TBS, de Freitas RD, Rodrigues ACBDC, Sousa LP, Sales CBS, Valverde LF, Soares MBP, Dos Reis MG, Coletta RD, Ramos EAG, Camara CA, Silva TMS, Filho JMB, Bezerra DP, Rocha CAG. β-Lapachone and its iodine derivatives cause cell cycle arrest at G2/M phase and reactive oxygen species-mediated apoptosis in human oral squamous cell carcinoma cells. Free Radic Biol Med. 2018;126:87-100. DOI: 10.1016/j.freeradbiomed.2018. 07.022.

[54] Zada S, Hwang JS, Ahmed M, Lai TH, Pham TM, Kim DH, Kim DR. Protein kinase A activation by β Lapachone is associated with apoptotic cell death in NQO1 overexpressing breast cancer cells. Oncol Rep. 2019;42: 1621-1630. DOI: 10.3892/or.2019.7243.

[55] Zhang Q, Chen L, Hu LJ, Liu WY, Feng F, Qu W. Two new ortho benzoquinones from Uncaria rhynchophylla. Chin J Nat Med. 2016; 14:232-235. DOI: 10.1016/S1875-5364 (16)30021-8.

[56] Panthong K, Hongthong S, Kuhakarn C, Piyachaturawat P, Suksen K, Panthong A, Chiranthanut N, Kongsaeree P, Prabpai S, Nuntasaen N, Reutrakul V. Pyranonaphthoquinone and anthraquinone derivatives from Ventilago harmandiana and their potent anti-inflammatory activity. Phytochemistry. 2020;169:112182. DOI: 10.1016/j.phytochem.2019.112182.

[57] Yu HB, Yin ZF, Gu BB, Zhang JP, Wang SP, Yang F, Lin HW. Cytotoxic meroterpenoids from the marine sponge Dactylospongia elegans. Nat Prod Res. 2019:1-7. DOI: 10.1080/ 14786419.2019.1633644.

[58] Neupane RP, Parrish SM, Neupane J, Yoshida WY, Yip ML, Turkson J, Harper MK, Head JD, Williams PG. Cytotoxic sesquiterpenoid quinones and quinols, and an 11-membered heterocycle, Kauamide, from the Hawaiian marine sponge Dactylospongia elegans. Mar Drugs. 2019;17:423-428. DOI: 10.3390/ md17070423.

[59] Luo X, Li P, Wang K, de Voogd NJ, Tang X, Li G. Cytotoxic sesquiterpenoid quinones from South China Sea sponge Dysidea sp. Nat Prod Res. 2019;1-6. DOI: 10.1080/14786419.2019.1679132.

[60] Ito T, Nguyen HM, Win NN, Vo HQ, Nguyen HT, Morita H. Three new sesquiterpene aminoquinones from a Vietnamese Spongia sp. and their biological activities. J Nat Med. 2018;72: 298–303. DOI: 10.1007/s11418-017- 1130-5.

[61] Yen I, Lee SY, Lin KT, Lai FY, Kuo MT, Chang WL. In vitro anticancer activity and structural characterization of ubiquinones from Antrodia cinnamomea mycelium. Molecules. 2017;22:747-752. DOI: 10.3390/ molecules22050747.

[62] Li JL, Jiang X, Liu X, He C, Di Y, Lu S, Huang H, Lin B, Wang D, Fan B. Antibacterial anthraquinone dimers from marine derived fungus Aspergillus sp. Fitoterapia. 2019;133:1-4. DOI: 10.1016/j.fitote.2018.11.015.

[63] Wang M, Sun ZH, Chen YC, Liu HX, Li HH, Tan GH, Li SN, Guo XL, Zhang W. Cytotoxic cochlioquinone derivatives from the endophytic fungus Bipolaris sorokiniana derived from Pogostemon cablin. Fitoterapia. 2016;

110:77-82. DOI: 10.1016/j. fitote.2016.02.005.

[64] He W, Zhou XJ, Qin XC, Mai YX, Lin XP, Liao SR, Yang B, Zhang T, Tu ZC, Wang JF, Liu Y. Quinone/ hydroquinone meroterpenoids with antitubercular and cytotoxic activities produced by the sponge-derived fungus Gliomastix sp. ZSDS1-F7. Nat Prod Res. 2017;31:604-609. DOI: 10.1080/ 14786419.2016.1207076.

[65] Le Pogam P, Le Lamer AC, Siva B, Legouin B, Bondon A, Graton J, Jacquemin D, Rouaud I, Ferron S, Obermayer W, Babu KS, Boustie J. Minor Pyranonaphthoquinones from the Apothecia of the Lichen Ophioparma ventosa. J Nat Prod. 2016; 79:1005-1011. DOI: 10.1021/acs. jnatprod.5b01073.

[66] Zhang HM, Ju CX, Li G, Sun Y, Peng Y, Li YX, Peng XP, Lou HX. Dimeric 1,4-benzoquinone derivatives with cytotoxic activities from the marine-derived Fungus Penicillium sp. L129. Mar Drugs. 2019;17:383-389. DOI: 10.3390/md17070383.

[67] Mishra PD, Verekar SA, Deshmukh SK, Joshi KS, Fiebig HH, Kelter G. Altersolanol A: a selective cytotoxic anthraquinone from a Phomopsis sp. Lett Appl Microbiol. 2015;60:387-391. DOI: 10.1111/lam.12384.

[68] Otto C, Hahlbrock T, Eich K, Karaaslan F, Jürgens C, Germer CT, Wiegering A, Kämmerer U. Antiproliferative and antimetabolic effects behind the anticancer property of fermented wheat germ extract. BMC Complement Altern Med. 2016;1;16:160. DOI: 10.1186/s12906-016-1138-5.

[69] Ge X, Sun C, Feng Y, Wang L, Peng J, Che Q, Gu Q, Zhu T, Li D, Zhang G. Anthraquinone Derivatives from a Marine-Derived Fungus Sporendonema casei HDN16-802. Mar Drugs. 2019;17: 334. DOI: 10.3390/md17060334.

[70] Li JS, Zhang H, Qi H, Wang JD, Xiang WS. Bioactive naphthoquinone and anthrone derivatives from endophytic Micromonospora sp. NEAUgq13. J Asian Nat Prod Res. 2019;21: 1151-1160. DOI: 10.1080/ 10286020.2018.1520222.

Medicines. 2017;15:944-949. DOI: 10.1016/s1875-5364(18)30011-6.

activity of primin and primincontaining extracts from Miconia willdenowii. Fitoterapia. 2019;138:

104297. DOI: 10.1016/j. fitote.2019.104297.

inermis (henna), produces

10.1007/s11033-019-05218-3.

[81] Carcamo-Noriega EN, Sathyamoorthi S, Banerjee S, Gnanamani E, Mendoza-Trujillo M, Mata-Espinosa D, Hernández-Pando R, Veytia-Bucheli JI, Possani LD,Z are RN. 1, 4-Benzoquinoneantimicrobial agents against Staphylococcus aureus and Mycobacterium tuberculosis derived from scorpion venom. Proc Natl Acad Sci U S A. 2019;116:12642-12647. DOI:

10.1073/pnas.1812334116.

**63**

[77] Viegas FPD, Espuri PF, Oliver JC, Silva NC, Dias ALT, Marques MJ, Soares MG. Leishmanicidal and antimicrobial

*DOI: http://dx.doi.org/10.5772/intechopen.95598*

*Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism*

[78] Xavier MR, Santos MMS, Queiroz MG, de Lima Silva MS, Goes AJS, De Morais Jr MA. Lawsone, a 2-hydroxy-1, 4-naphthoquinone from Lawsonia

mitochondrial dysfunctions and triggers mitophagy in Saccharomyces cerevisiae. Mol Biol Rep. 2020;47:1173-1185. DOI:

[79] Balansa W, Mettal U, Wuisan ZG, Plubrukarn A, Ijong FG, Liu Y, Schäberle TF. A new sesquiterpenoid aminoquinone from an Indonesian marine sponge. Mar drugs. 2019;17: 158-163. DOI: 10.3390/md17030158.

[80] Narmani A, Teponno RB, Arzanlou M, Surup F, Helaly SE, Wittstein K, Praditya DF, Babai-Ahari A, Steinmann E, Stadler M. Cytotoxic, antimicrobial and antiviral secondary metabolites produced by the plant pathogenic fungus Cytospora sp. CCTU A309. Fitoterapia. 2019;134:314-322. DOI: 10.1016/j.fitote.2019.02.015.

[71] Xu C, Sun X, Jin M, Zhang X. A novel benzoquinone compound isolated from deep-sea hydrothermal vent triggers apoptosis of tumor cells. Mar Drugs. 2017;15:200-206. DOI: 10.3390/ md15070200.

[72] Carretero-Molina D, Ortiz-López FJ, Martín J, Oves-Costales D, Díaz C, de la Cruz M, Cautain B, Vicente F, Genilloud O, Reyes F. New Napyradiomycin Analogues from Streptomyces sp. Strain CA-271078. Mar Drugs. 2019;18:22. DOI: 10.3390/md18010022.

[73] Nain-Perez, A, Barbosa LC, Rodríguez-Hernández D, Kramell AE, Heller L, Csuk R. Natural abenquines and synthetic analogues: preliminary exploration of their cytotoxic activity. Bioorg Med Chem Lett. 2017;27: 1141-1144. DOI: 10.1016/j. bmcl.2017.01.079.

[74] Zhou B, Jiang YJ, Ji YY, Zhang HJ, Shen L. Lactoquinomycin C and D, two new medermycin derivatives from the marine-derived Streptomyces sp. SS17A. Nat Prod Res. 2020;34:1213-1218. DOI: 10.1080/14786419.2018.1556265.

[75] Abdelfattah MS, Elmallah MI, Mohamed AA, Ishibashi M. Sharkquinone, a new ana-quinonoid tetracene derivative from marinederived Streptomyces sp. EGY1 with TRAIL resistance-overcoming activity. J Nat Med. 2017;71:564-569. DOI: 10.1007/s11418-017-1086-5.

[76] Farooq U, Khan S, Naz S, Khan A, Khan A, Ahmed A, Riaz N. Three new anthraquinone derivatives isolated from Symplocos racemosa and their antibiofilm activity. Chin J Nat

*Cytotoxic and Antimicrobial Activities of Quinones Isolated from Different Organism DOI: http://dx.doi.org/10.5772/intechopen.95598*

Medicines. 2017;15:944-949. DOI: 10.1016/s1875-5364(18)30011-6.

[77] Viegas FPD, Espuri PF, Oliver JC, Silva NC, Dias ALT, Marques MJ, Soares MG. Leishmanicidal and antimicrobial activity of primin and primincontaining extracts from Miconia willdenowii. Fitoterapia. 2019;138: 104297. DOI: 10.1016/j. fitote.2019.104297.

[78] Xavier MR, Santos MMS, Queiroz MG, de Lima Silva MS, Goes AJS, De Morais Jr MA. Lawsone, a 2-hydroxy-1, 4-naphthoquinone from Lawsonia inermis (henna), produces mitochondrial dysfunctions and triggers mitophagy in Saccharomyces cerevisiae. Mol Biol Rep. 2020;47:1173-1185. DOI: 10.1007/s11033-019-05218-3.

[79] Balansa W, Mettal U, Wuisan ZG, Plubrukarn A, Ijong FG, Liu Y, Schäberle TF. A new sesquiterpenoid aminoquinone from an Indonesian marine sponge. Mar drugs. 2019;17: 158-163. DOI: 10.3390/md17030158.

[80] Narmani A, Teponno RB, Arzanlou M, Surup F, Helaly SE, Wittstein K, Praditya DF, Babai-Ahari A, Steinmann E, Stadler M. Cytotoxic, antimicrobial and antiviral secondary metabolites produced by the plant pathogenic fungus Cytospora sp. CCTU A309. Fitoterapia. 2019;134:314-322. DOI: 10.1016/j.fitote.2019.02.015.

[81] Carcamo-Noriega EN, Sathyamoorthi S, Banerjee S, Gnanamani E, Mendoza-Trujillo M, Mata-Espinosa D, Hernández-Pando R, Veytia-Bucheli JI, Possani LD,Z are RN. 1, 4-Benzoquinoneantimicrobial agents against Staphylococcus aureus and Mycobacterium tuberculosis derived from scorpion venom. Proc Natl Acad Sci U S A. 2019;116:12642-12647. DOI: 10.1073/pnas.1812334116.

**65**

**Chapter 4**

**Abstract**

**1. Introduction**

Some Methodological Aspects in

Studies of Metal Nanoparticles'

Toxicity towards Cultured Cells

*Elena Mikhailovna Egorova and Said Ibragimovich Kaba*

tant molecules and micelles into the total effect on cell viability.

particle size effect, zeta potential, toxicity of surfactants

**Keywords:** metal nanoparticles, cytotoxicity, methodological aspects,

Some actual questions arising in studies of the toxic effects of metal nanoparticle water solutions on cultured cells are considered. *First*, basic conditions required for the correct determination of nanoparticle size effect; the arguments are adduced in favor of the use of number nanoparticle concentration instead of the conventional mass one. *Second*, the problem of invalidity of the Smoluchowski equation; for charged nanoparticles the error in zeta potential value calculated from the measured electrophoretic mobility by the Smoluchowski equation cannot be neglected. *Third,* for the nanoparticles stabilized with surfactants, elucidation of the mechanism of cytotoxicity should include the determination of separate contributions of surfac-

In the last decades, the intensive development of medical applications of silver, gold and other metal nanoparticles brings into light the problem of their toxicity for a human organism. Therefore, studies on the biological activity of these nanoparticles are oriented mostly on elucidation of the mechanisms of their toxic effects on living organisms and determination of the conditions providing their safe usage. These studies lie within the scope of new branch in toxicology – nanotoxicology; general information about this direction may be found in several reviews [1–3]. One of the main lines of studies in nanotoxicology is focused on the toxicity of silver nanoparticles (AgNPs) used as water solutions. The reason lies in the widespread applications of these nanoparticles for medical purposes due mostly to their expressed antimicrobial activity; some recent results in this field are summarized in [4–6]. Studies are fulfilled mainly on the three objects: microorganisms, cultured cells and animals (mice and rats). The results obtained in the last two decades are presented in a great number of original papers, reviews and books; several examples are given in [7–9]. Nevertheless, one can conclude that there is no clearness in the main questions important for the estimation of AgNPs safety for a human organism. Analysis of the literature as well as our long-term experience in studies of AgNPs biological effects allow to infer that the main reason lies in the field of methodology. *First*, there is a wide variety of factors affecting the main toxicity criteria, one

## **Chapter 4**
