Strategies to diversify natural products for drug discovery

Abstract

Natural product libraries contain specialized metabolites derived from plants, animals, and microorganisms that play a pivotal role in drug discovery due to their immense structural diversity and wide variety of biological activities. The strategies to greatly extend natural product scaffolds through available biological and chemical approaches offer unique opportunities to access a new series of natural product analogues, enabling the construction of diverse natural product-like libraries. The affordability of these structurally diverse molecules has been a crucial step in accelerating drug discovery. This review provides an overview of various approaches to exploit the diversity of compounds for natural product-based drug development, drawing upon a series of examples to illustrate each strategy.

7‐Deoxynarciclasine shows promising antitumor efficacy by targeting Akt against hepatocellular carcinoma

“…Natural products possessing diverse chemical structures and biological functions usually serve as major new leads source of for pharmaceutical development, and approximately half of the pharmaceuticals in drug discovery today are derived from natural products and their derivatives . 7‐deoxynarciclasine (7‐DONCS), an active narciclasine alkaloid from Lycoris radiata (Amaryllidaceae), exhibits various biological effects, including anticancer, plant growth‐inhibitory, anti‐Alzheimer's disease and antiparasitic activities.…”

Free Marine Natural Products Databases for Biotechnology and Bioengineering

“…[16,52] MNP research for bioactive compounds is very fruitful and from 1985 to 2012 at least 4196 bioactive compounds were described. [4] Bioactive MNPs can present properties [52][53][54] such as anticancer, [55][56][57][58] antimicrobial, [59,60] antiviral, [61] anti-Alzheimer, [62] anti-inflammatory, [63,64] drug delivery, [65] and biosurfactants. [66] This success determines the high demand for MNPs in pharmaceutical sciences.…”

P450 Monooxygenases Enable Rapid Late‐Stage Diversification of Natural Products via C−H Bond Activation

“…Their structural complexity and diversity are unmatched, and arise from a constant evolutionary refinement by host organisms ,. Similarly, efficient natural product diversification is essential in the field of drug discovery, in order to meet the demand for novel drugs and drug analogues with improved specificity, or to test their metabolism in the body . This occurs preferably using chemical late‐stage modifications .…”

“…However, their diversity and complexity are a gift and a curse at the same time. Their quality as lead molecules is likely to be suitable, but effective diversification is essential in order to improve their drug quality . The latter often proves to be challenging.…”