Phytochemicals in Drug Discovery-A Confluence of Tradition and Innovation

Abstract

Phytochemicals have a long and successful history in drug discovery. With recent advancements in analytical techniques and methodologies, discovering bioactive leads from natural compounds has become easier. Computational techniques like molecular docking, QSAR modelling and machine learning, and network pharmacology are among the most promising new tools that allow researchers to make predictions concerning natural products' potential targets, thereby guiding experimental validation efforts. Additionally, approaches like LC-MS or LC-NMR speed up compound identification by streamlining analytical processes. Integrating structural and computational biology aids in lead identification, thus providing invaluable information to understand how phytochemicals interact with potential targets in the body. An emerging computational approach is machine learning involving QSAR modelling and deep neural networks that interrelate phytochemical properties with diverse physiological activities such as antimicrobial or anticancer effects.

Keywords: natural products; phytochemicals; traditional medicine.

Figure 1

Phytochemicals used as drugs. Apomorphine (1), arteether (2) and galantamine (3).

Figure 2

Synthetic small molecule drugs approved by the FDA in 2023. Bexagliflozin (Brenzavvy^TM) (4), sotalgliflozin (Inpefa^TM) (5), zuranolone (Zurzuvae^TM) (6), and vamorolone (7) (Agamree^TM).

Figure 3

Phytochemicals found in Filsuvez^TM are composed of a mixture of pentacyclic triterpenes betulin (8), lupeol (9), betulinic acid (10), erythrodiol (11), and oleanolic acid (12) [23].

Figure 4

The sesquiterpene germacrone (13), synergistic with the antiviral agent oseltamivir.

Figure 5

Phytochemicals showing anti-HIV potential adapted from [39]. Created with BioRender.com.

Figure 6

The co-delivery of phytochemicals in cancer therapy * adapted from [52], created with BioRender.com.

Figure 7

Chemical structures of taxane (14), ellipticine (15), camptothecin (16), combretastatin (17), curcumin (18), podophyllotoxin (19), homoharringtonine (20).

Figure 8

Phytochemicals and their mechanisms of action against drug resistance in microorganisms adapted from [22,79]. Created with BioRender.com.

Figure 9

Sequential Stages in Phytochemical Drug Discovery and Development.

Figure 10

Chemical structures of liquiritin (21), apigenin (22), quercetin (23), luteolin (24), and neoandrographolide (25).

Figure 11

Bayogenin (26) asiatic acid (27), and andrographolide (28), potential leads against HK2.

Figure 12

The phytochemical demethylzeylasteral (29) is a glucocorticoid receptor antagonist.