**2. The biological activities of secondary metabolites**

Unique structural diversity is provided by natural products when compared with standard combinatorial chemistry; these give opportunities for discovering novel lead compounds with low molecular weight. The world's biodiversity evaluation of natural products for potential biological activity is less than 10%; thus, a lot of useful novel natural lead compounds await discovery [37].

Terrestrial plants are the major source of secondary metabolites; other sources include fungi, bacteria, as well as several marine organisms [10].

#### **2.1 The pharmacological activity of plant-derived secondary metabolites**

#### *2.1.1 Antibacterial activity*

Natural antibiotics are secondary metabolites produced by microbes that inhibit bacterial growth by targeting essential cellular processes such as the synthesis of the

#### *Secondary Metabolites: The Natural Remedies DOI: http://dx.doi.org/10.5772/intechopen.101791*

bacterial cell wall, DNA/RNA, and proteins. They are not essential for the growth of the organism (and usually produce at the end of the exponential phase of their growth). They have diverse roles, such as in cellular differentiation, nutrient sequestration, metal transport, ecological interactions, and defense [38, 39].

Between 1935 and 1968, 12 classes of antibiotics were launched and approved for use as drugs. However, between 1969 and 2000, the number dropped markedly, with only two classes introduced. Out of the 30 antibiotics launched between the year 2003 and 2015, 16 belong to natural products and their derivatives. They include three new classes of natural antibiotics—two actinomycete: the lipopeptide daptomycin in 2003 and fidaxomicin (of the tiacumicin family) in 2010. The third is a fungal product: retapamulin derived from pleuromutilin and approved in 2007 for topical use [38, 40].

Newman and Cragg reported the introduction of several natural secondary metabolites that have been reported to possess potent antibacterial activity including: anthrasil, omadacycline, dalbavacin, plazomicin, ceftaroline fasamil acetate, lefamulin, sarecycline, eravacycline imi-cilast-relebactam, etc. [41].

#### *2.1.2 Anti-inflammatory activity*

Inflammation is a normal biological process that occurs as a response to microbial infection, chemical irritation, or tissue injury. It is usually initiated by moving the immune cells from blood vessels and release of mediators to the damage site. It is then followed by reinforcement with inflammatory cells, release of reactive oxygen species (ROS), reactive nitrogen species (RNS), and proinflammatory cytokines to fight the foreign pathogens and repairing the injured tissues. In general, normal inflammation is rapid and self-limiting, but unresolved and prolonged inflammation causes various chronic disorders. As a pathologic condition, inflammation can include a wide range of diseases such as rheumatic and immune-mediated conditions, diabetes, cardiovascular accident, etc. [38, 42]. Aswad and coworkers reported the use of moupinamide, capsaicin, and hypaphorine—natural products—with high scores in their indexing of potential anti-inflammatory drug candidates [43]. Mona et al. also reported more than 15 herbs, where their anti-inflammatory effects have been evaluated in clinical and experimental studies including *Curcuma longa*, *Zingiber officinale*, *Rosmarinus officinalis*, *Borago officinalis* [42].

#### *2.1.3 Anticancer activity*

Cancer is one of the leading causes of death (second to cardiovascular diseases) in the world, despite the availability of wide range of anticancer drugs. The estimated cancer burden in the world as reported by the World Health Organization (WHO) is 18.1 million new cases and 9.6 million deaths as at 2018 [38, 44]. Presently, research efforts are directed toward the discovery of natural products with anticancer potential [45]. Several secondary metabolites have been reported to possess anticancer potential; some of these compounds have the capacity to prevent oxidative stress and inflammation that causes damage to DNA, which in turn leads to carcinogenesis [45]. Natural products such as irinotecan, vincristine, vinblastine, etoposide, and paclitaxel from plants, actinomycin D and mitomycin C from bacteria as well as marine-derived bleomycin are widely used in the treatment of various cancers [44].

Also, fruits and vegetables are plant sources that are known to contain vitamins, minerals, folate, plant sterols, carotenoids, and various phytochemicals such as

flavonoid and polyphenols—natural product compounds that are associated with reduced cancer mortality and risk [46]. The critical relationship of fruit and vegetable intake and cancer prevention has been thoroughly documented. It has been suggested that major public health benefits could be achieved by substantially increasing consumption of these foods [38].

Herbs and spices such as ginger, capsicum, curcumin, clove, rosemary, sage, oregano, and cinnamon are very rich in antioxidants due to the high content of phenolic compounds and have been shown to counteract reactive oxygen species (ROS) mediated damage in different human cancers [47]. Many cyclic peptides and their derivatives obtained from marine organisms have been shown to possess anticancer, antimicrobial, anti-inflammatory, antiproliferative, and antihypertensive properties [46]. Furthermore, lactoferrin, a multifunctional protein found in bovine and camel milk, has also been reported to possess anticancer effect [48].

#### *2.1.4 Antiviral activity*

Natural compounds are an important source for the discovery and the development of novel antiviral drugs because of their availability and expected low side effects. Naturally occurring compounds with antiviral activity have been recognized as early as 1940s. The search for effective drugs against human immunodeficiency virus (HIV) is the need of hour. Most of the work related with antiviral compounds revolves around inhibition of various enzymes associated with the life cycle of viruses. Structure-function relationship between secondary metabolites and the HIV enzyme inhibitory activity has been observed [38].

#### *2.1.5 Hepatoprotective activity*

Diseases of the liver have been classified as high priority areas of health care, as an estimate by the World Health Organization shows approximately 500 million people of the world are suffering from a severe form of liver disorders that may lead to chronic hepatitis. Hepatic disorders can be caused by exposure to agents such as drugs, viruses, parasites, and toxins. Such an exposure usually may result in degeneration and inflammation of the liver; furthermore, it results in fibrosis and cirrhosis [49]. In addition, different chronic diseases such as diabetes may lead to development of hepatic clinical manifestations.

Several flavonoids such as catechin, apigenin, quercetin, naringenin, rutin, and venoruton are reported for their hapatoprotective activities [38]. Muhammad and coworkers review studies conducted on the composition, pharmacology, and nature of some selected plants in the light of possible mechanism deduced from experimental trials [49]. Also, a comprehensive review by Meng et al. [50], listed several plants and products that have been used in the prevention and treatment of chemically induced liver damages [50].

#### *2.1.6 Important present-day drugs derived from plants secondary metabolites*

Many drugs with wide range of pharmacological activities were derived from alkaloids [51]. Some of the important drugs derived from alkaloids include:

1.Quinine—antimalaria [51]

2.Morphine—analgesic [52]

*Secondary Metabolites: The Natural Remedies DOI: http://dx.doi.org/10.5772/intechopen.101791*


#### *2.1.7 The pharmacological activities of cardiac glycosides*

The effects of cardiac glycosides mainly for increasing heart muscle force of contraction and reducing heart rate are beneficial for treating cardiac arrhythmias and congestive heart failure; cardiac glycosides have long been used to manage these ailments. The commonest cardiac glycosides used clinically include digoxin, digitoxin, ouabain, and bufalin [61]. Other forms of cardiac glycosides are antiarin, thevetin A and B, peruvoside, neriifolin, thevetoxin, ruvoside, theveridoside, cerberin, convallarin, convallamarin, convallatoxin, glucoscillarene A, proscillaridine A, scillarene A, scilliglaucoside and scilliphaeoside, marinobufagenin, oleandrin, folineriin, adynerin, digitoxigenin, marinobufagenin, telocinobufagin [62]. Among these substances, literature has also reported the therapeutic uses of acetyldigoxin, digitoxin, digoxin, gitoformate, gitoxin, lanatoside C, metildigoxin (β-methyldigoxin), ouabain (strophanthin-g), peruvoside, proscillaridin, strophanthin-k [63], apart from digoxin, digitoxin, ouabain, and bufalin earlier mentioned [61].

#### *2.1.8 The pharmacological activities of flavonoids and phenolic compounds*

From plants, over 8000 phenolic compounds have been reported [64]. Interestingly, flavonoids make up half of these phenolic compounds [64]. Effectively, flavonoids and several other phenolic compounds have been reported to possess antibacterial, anti-inflammatory, antioxidants, anticancer, cardioprotective, immunomodulatory, and skin radioprotective effects from UV light. More so, these compounds are good pharmaceutical candidates for medical application [65]. Several flavonoids including apigenin, galangin, flavone and flavonol glycosides, isoflavones, flavanones, and chalcones have been shown to possess potent antibacterial activity [38].

#### *2.1.9 The pharmacological activities of tannins*

Certain carcinogenic incidences, such as esophageal cancer, have been related to tannins-rich foods consumption, especially the herbal tea and betel nuts. However, several reports showed that tannins' carcinogenic effects are not due to tannins themselves but likely due to components associated with the tannins [66]. Many literatures revealed negative association between cancer incidences and consumption of tannins components and tea polyphenols, suggesting their anticarcinogenic effects [66].

The antimutagenic and antimicrobial activities of tannins have been documented. Tannins inhibit the growth of viruses, bacteria, yeast, and many fungi. It has also been reported that propyl gallate and tannic acid inhibit aquatic bacteria and foodborne bacteria; this action is not reported for gallic acid. In food processing industry, catfish fillets' shelf-life can be enhanced using the tannic acid antimicrobial property. The antihypertensive, hypolipidemic, coagulative, and immunomodulatory effects of tannins have been reported [66].

#### *2.1.10 The pharmacological properties of terpenoids*

Terpenoids being the most abundant compounds in natural products have been reported to possess antibacterial, antimalarial, antiviral, hypoglycemic, neuroprotective, and anti-inflammatory activities. Furthermore, literatures have also documented the effects of terpenoids in treating and preventing cardiovascular diseases, antioxidation, immunoregulation, and promotion of transdermal absorption of substances [67].

#### **2.2 The pharmacological activities of fungal-derived secondary metabolites**

#### *2.2.1 Some important drugs of fungal origin*

#### *2.2.1.1 Antibiotics*

The beginning was the discovery of penicillin by Alexander Fleming from penicillium mold; penicillin is one of the most known antibiotics in use, and the beta lactam antibiotics penicillin and cephalosporin were all derived from fungus [68]. Other antibiotics derived from fungus include alamethicin, brefeldin A, aphidicolin, citromycin, fumagillin, cerulenin, eupenifeldin, fusidic acid, fusafungine, itaconic acid, usnic acid, helvolic acid, nigrosporin B, verrucarin A, vermiculine, etc. [68]. Tiamulin, retaparmulin, and valnemulin are antibiotics derived from pleuromutilin [68].

#### *2.2.1.2 Antifungal agents*

Antifungal griseofulvin is a derivative of penicillium species [69], azoxystrobin, echinocandins, strobilurin, micafungin, anidulafungin, and caspofungin are all antifungal agents originally derived from fungus [70].

#### *2.2.1.3 Immunosuppressive agents*

Bredinin, cyclosporin, mycophenolic acid, myriocin, endocrocin, and gliotoxin are all immunosuppressants isolated from fungus [71].

## *2.2.1.4 Potential antiviral agents*

Compounds from several mushrooms such as *Ganoderma lucidum*, *Grifola frondose*, *Garnoderma colossus*, *Lentinus edodes*, *Hypsizygus marmoreus*, *Scleroderma citrinum*, *Cordyceps militaris*, *Trametes versicolor*, *Flammulina velutipes*, *Fomitopsis officinalis* are under research for potential antiviral activities validations [72, 73].
