“Drug-likeness” properties of natural compounds

Abstract

<jats:title>Abstract</jats:title> <jats:p>Our previous work was focused on the fundamental physical and chemical concepts behind “drug-likeness” and “natural product (NP)-likeness”. Herein, we discuss further details on the concepts of “drug-likeness”, “lead-likeness” and “NP-likeness”. The discussion will first focus on NPs as drugs, then a discussion of previous studies in which the complexities of the scaffolds and chemical space of naturally occurring compounds have been compared with synthetic, semisynthetic compounds and the Food and Drug Administration-approved drugs. This is followed by guiding principles for designing “drug-like” natural product libraries for lead compound discovery purposes. In addition, we present a tool for measuring “NP-likeness” of compounds and a brief presentation of machine-learning approaches. A binary quantitative structure–activity relationship for classifying drugs from nondrugs and natural compounds from nonnatural ones is also described. While the studies add to the plethora of recently published works on the “drug-likeness” of NPs, it no doubt increases our understanding of the physicochemical properties that make NPs fall within the ranges associated with “drug-like” molecules.</jats:p>

In silico analysis of Phyllanthus amarus phytochemicals as potent drugs against SARS-CoV-2 main protease

“…All other compounds showed between two and four violations; however, studies have shown that if a natural product is used as a guiding structure for the production of a synthetic drug such that molecular descriptors (like MW, clogP etc.) can be controlled, that is, the best of both natural and synthetic compounds can be taken into account to obtain a drug that is both harmless to the human body and effective on the virus [ 76 ]. Based on this range, all the 16 compounds qualify as drug-like compounds with nRB values lesser than and equal to 10 [ 77 , 78 ].…”

Computational Study on Temperature Driven Structure–Function Relationship of Polysaccharide Producing Bacterial Glycosyl Transferase Enzyme

“…The drug-likeness model score of the UDP-Glucose ligand was found to be 0.93, as might be observed in Figure 4 A. Drug likeliness is a complex qualitative factor that determined bioavailability of a ligand for its substrate [ 65 ]. A positive scoring indicates our ligand fit for the substrate interaction.…”

Cheminformatic Characterization of Natural Antimicrobial Products for the Development of New Lead Compounds

“…Drug-likeness is a quantitative concept used to describe molecules that possess functional groups, chemical and physicochemical properties consistent with most of the approved drugs [ 71 , 72 ]. It provides an insight into the early identification of chemical compounds that are “most likely to succeed” in the drug development venture.…”

“…Natural products, chemical entities produced by living organisms, tend to break these established drug-likeness rules obtained from synthetic chemical libraries. The concept of natural product-likeness has been reported to have the potential to open new opportunities for drug discovery from natural compounds while neglected by the drug-likeness rule [ 72 ].…”