**3.2 Antifungal properties**

Resistance to antifungal drugs has been spread in recent years. Resistance to antifungal drugs has led to increased morbidity and mortality. Since the molecular mechanisms in humans and fungi are so similar, there is always the possibility that the fungal cytotoxic agent is toxic to host cells. As a result, patients with compromised immune systems, such as transplants, cancer patients, and diabetics, who do not respond effectively to current antifungal treatments, need new antifungal therapies. Antifungal drugs currently used to treat fungal infections have significant side effects such as itching, diarrhea, vomiting, *etc*. In addition, it is less effective because of the development of drug resistance by the many fungi [112, 113]. The alkaloids protoberberine jatrorrhizine, isolated from *Mahonia aquifolium,* were the most potent inhibitory antifungal activity [114]. (+)-Cocsoline is a bisbenzylisoquinoline alkaloid isolated from epinetrumvillosum whose antifungal action has been demonstrated [115]. The alkaloids N-ethylhydrasteinehydroxylactam and 1-methoxyberberine chloride isolated from *Corydalis longipes* have been shown to have significant inhibitory action [116]. *Glaucium oxylobum* produced four alkaloids: dicentrine, glaucine, protopine, and alpha-allocryptopin exhibited antifungal activity against *Microsporumgypseum*, *Microsporumcanis*, *T. mentagrophytes*, and *Epidermophytonfloccosum* [117]. Canthin-6-one and 5-methoxy-canthin-6-one from *Zanthoxylumchiloperone* var. *angustifolium* are antifungal against *Candida albicans*, *Aspergillus fumigatus*, and *T. mentagrophytes* [118]. Frangulanine, a cyclic peptide alkaloid, and waltherione A, quinolinone alkaloids derived from *Melochiaodorata* have been shown to antifungal activity against a wide range of pathogenic fungi [119]. Additionally, anodic alkali aninolinate has been shown to have antifungal

action [120]. Two antimyctic fructoxin alkaloids have been identified from the root of Dictamnusdasycarpus. 3-Methoxisampangin from cleistopholispatens significantly inhibits *C. albicans*, *A. fumigatus*, and *C. neoformans* [121]. A new alkaloid, 2-(3,4-dimethyl-2,5-dihydro-1H-pyrrol-2-yl)-1-methylethyl pentanoate, was isolated from the plant *Datura metel* has shown *in-vitro* and *in-vivo* action against *Aspergillus* and *Candida species* [122]. Fungi toxic action was demonstrated for alkaloids isolated from *Ruta graveolens* L., Tomadini Glycoalkaloids isolated from tomatoes, cannabinoid alkaloid, isoquinoline, methaqualone, flavonol, and gallic acid [123, 124].

#### **4. Anticancer potential of secondary metabolites**

Cancer is the cause of death worldwide; experts are developing new therapies less likely to cause side effects. Cancer is one of the most severe health concerns, despite substantial advances in cancer therapy [125]. Several new secondary metabolites from plants are discovered each year, opening new avenues for research in the fight against cancer. Plant secondary metabolites have substantially contributed to this topic, which has been at the heart of herbal medicines. Plant's secondary metabolites have been shown to have anticancer effects, such as the ability to reduce cancer cell growth and development, kill cancer cells, and fight against multi-drug resistance in certain malignancies [126]. Plant secondary metabolites are thought to be helpful in drug development. The secondary plant metabolites are presently used in clinical and undergoing clinical trials as anticancer therapies [127, 128].

For thousands of years, humans have used herbs to treat certain diseases. Researchers are particularly interested in generating anticancer drugs from the plant's secondary metabolites. Plant secondary metabolites such as flavonoids, polyphenols, anthraquinones, triterpenoids, alkaloids, terpenoids, quinones, and others play an essential role in cancer prevention [129]. Flavonoids (6,7,30-trimethoxy-3,5,40 trihydroxy-flavone and 5,40-dihydroxy-3,6,30-trimethoxy-flavone 7-O- -d-glucoside) isolated from *Chrysosplenium nudicaule Spearmary* was reported as cytotoxic and antitumor activities in cancer cell growth of human leukemia and gastric cancer cell lines [130, 131]. The agathisflavone induces apoptosis and antiproliferative effect on the development of leukemia cells. Citrus flavonoids have a profound inhibitory effect on the development of leukemia cells. Other research suggests that quercetin may act as an antiproliferative agent by inhibiting cell proliferation, growth, and cell cycle termination [132, 133]. Studies of Kaempferol and quercetin have shown antiproliferative action by inhibiting the development of the human colon (HT-29, COLO 201, and LS-174T), breast (MCF-7 ADRr), and ovarian (OVCA 433) cancer cell lines [134–136]. In addition, quercetin inhibited the G1 phase of the cell cycle in human leukemic T-cells and human gastric cancer cells [137, 138]. In a human oral squamous carcinoma cell line (SCC-25), quercetin had a biphasic effect on cell growth and proliferation [139]. On the other hand, *in-vivo* research on quercetin has yielded consistent findings, indicating a promising chemopreventive drug against skin cancer [140]. In contrast, kaempferol treatment of the human lung cancer cell line A549 resulted in a dosage and time-dependent decrease in cell survival and DNA synthesis. While Kaempferol dramatically decreased the number of breast cancer cells (MCF-7) viable estrogen receptor-positive [141, 142].

Phenolic compounds are one of the most diverse and widespread groups of plant metabolites, and they have a wide range of biological roles in regulating carcinogenesis [143]. Polyphenols have several advantages as anticancer drugs, including high

#### *Plant Secondary Metabolites: Therapeutic Potential and Pharmacological Properties DOI: http://dx.doi.org/10.5772/intechopen.103698*

accessibility, minimal toxicity, and broad biological effects. The main advantage of polyphenols as anticancer drugs is cytotoxic effects on malignant cells growth [144, 145]. Many polyphenols have an anticancer effect in various cancer models, regardless of their different modes of action [146, 147]. Polyphenols of strawberries, including anthocyanins, Kaempferol, quercetin, coumaric acid esters, and ellagic acid esters, have been shown to inhibit the development of human oral and breast colon and prostate cancer cell lines [148]. The primary polyphenol of green tea, epigallocatechin-3-gallate (EGCG), is anticancer in various cancer types [149]. Researchers suggested that EGCG regulation may stimulate the production of reactive oxygen species and inhibit angiogenesis in cancer cells by regulating different pathways, such as AMP-activated protein kinase, epidermal growth factor receptor, insulin-like growth factor receptor, extracellular signal-regulated kinase, cyclin D1, Akt, STAT3, Wnt, and mTOR signaling in cancer cells [150–152]. A key ingredient of *Plumbago zeylanica* naphthoquinone has been shown *in-vitro* and *in-vivo* anticancer effective against various malignancies, including breast, pancreatic, lung, prostate, melanoma, and leukemia [153]. Cardanol, anacardic acid, and methyl cardol have been shown to decrease the cell growth of Hela cells and pituitary adenoma cells [154, 155]. In addition, anacardic acid-induced polymerase breakage, cell arrest, and regulation of apoptosis and anti-apoptotic proteins [156]. Furthermore, *in-vivo* investigations have confirmed plant-derived phenolic compounds' anticancer activity [157]. Colon, lung, breast, liver, prostate, stomach, esophagus, small intestine, pancreas mammary gland, and skin cancers are using xenograft animal models [158]. In another study of cyanidin-3-glucoside (C3G), the major anthocyanin in blackberry was investigated for the inhibition of 7,12-dimethylbenz[a]anthracene (DMBA)-12-O-tetradecanolyphorbol-13-acetate (TPA)-induced skin papillomas in an animal model [159]. Similarly, natural anthraquinones, such as rhein and emodin, have antitumor properties [160]. Tetrahydroanthraquinones, a kind of anthraquinone, inhibit cell proliferation, invasion, metastasis, and angiogenesis by apoptosis and cell cycle arrest. Altersolanol A (tetrahydroanthraquinone) has anticancer properties against bladder, colon, and stomach cancer. Moreover, Altersolanol A anticancer efficacy is linked to its pro-apoptotic and antiinvasive properties. A study reported that Altersolanol A has anticancer potential by reducing angiogenesis *in-vitro* and *in-vivo* [161, 162]. In addition, Altersolanol F reduced the viability of colorectal and cervical cancer cells, while Altersolanol N has cytotoxic effect against murine cancer cell line (L5178Y) [163, 164]. Likewise, several investigations have demonstrated catechins as antiproliferative properties in breast, colon, melanoma, and prostate cancer cells [165–167].

Isoquinoline alkaloid is a major alkaloid class with an anticancer effect in different cancer cells. Isoquinoline alkaloids are naturally isolated from the roots, and the bark of *Coptis chinensis* are important sources of [168]. Studies found that protoberberines (isoquinoline alkaloids) have significant anticancer potential in the treatment of gastric cancer [169]. Similarly, berberine alkaloid has been reported to have anticancer effects by suppressing the ERK/JNK/p38 MAPK/mTOR/p70 ribosomal S6 protein kinase and PI3K/Akt signaling pathways in cancer studies [170]. Tetrandrine (TET), a natural bis-benzylisoquinoline alkaloid, has shown anticancer activity against cancer cell lines. Tetrandrine-mediated cytotoxicity of chemotherapeutic drugs used to treat gastric cancer, including paclitaxel, 5-FU, oxaliplatin, and docetaxel [171, 172]. Piperlongumine, an amide alkaloid, has been shown anticancer by the intracellular ROS, p38/JNK signaling pathway [173, 174]. Hersutin alkaloid has been shown to induce apoptosis in HER2-positive and p53-mutated breast cancer cells [175]. Oxymatrine, a natural alkaloid isolated from the roots of *Sophora chrysophylla*, exhibits anticancer activity in human cervical cancer cells [176].

Terpenes are a broad category of secondary metabolites that include low polarity fragrant scaffolds and isoprene derivatives with various pharmacological activities, including anticancer activity. Triterpenoids have previously been shown to have anticancer properties in both *in-vitro* and *in-vivo* by nuclear factor-κβ (NF-κβ) and STAT3 signaling pathways [177]. The anticancer and narcotic activities of costunolide, a sesquiterpene lactone isolated from *Saussurea lappa,* have been demonstrated in gastrointestinal diseases [178]. Thymoquinone has been shown to slow the progression of diseases such as leukemia, breast adenocarcinoma, colorectal, pancreatic, prostate, and hepatic cancer [179]. The anticancer efficacy of thymoquinone against gastric cancer cells. Several other studies have shown that the combination of thymoquinone with 5-fluorouracil and cisplatin significantly improves the chemotherapeuticinduced anticancer effects in gastric cancer. Furthermore, thymoquinone has been shown to inhibit the Janus kinase (JAK)/STAT3 signaling pathway [180].
