Molecular Targets of Natural Drug Substances: Idiosyncrasies and Preferences

Abstract

All creatures – bacteria, plants, animals, humans – have many building blocks in common, down to biochemical structures and information processing languages. That is why natural substances seem to be better able to bind, and bind specifically, to drug targets in man, and to interact specifically with human biochemical networks. Property analyses of a large number of combinatorial and natural products and drugs have revealed the greater chemical similarity of the latter two. How about target preferences of natural products in comparison to synthetic drugs? On the basis of a comprehensive compilation and analysis of molecular targets of drug substances irrespective of their origin, the review categorises targets chemically and analyses the nature of drug targets. The dynamics of drug action are highlighted because an effective drug target comprises a biochemical system rather than a single molecule. The review is restricted to targets of natural compounds that are in use as therapeutic agents, comparing them with targets of marketed drugs in general. Differences are traced to historical, chemical, pharmacological, and social reasons. To give an example, the prevalence of natural products among antibacterial agents seems to be derived from, first, the necessity to have several hydrophilic binding sites for strong and lasting attachment to vital targets of bacteria, and synthetic drug candidates tend to be more hydrophobic than natural compounds. Second, other microorganisms are well equipped with – natural, of course – compounds with defensive or symbiotic functions that interfere with bacterial metabolism.

natural products - target classes - molecular mechanisms - drug substances

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1 History
This article is based on lectures held at the 7th Joint Meeting of AFERP, ASP, GA, PSE & SIF, Athens, Greece, August 2008, and at the PharmSciFair Conference, Medicinal Plant and Natural Product Research Session, Nice, France, June 2009.