Molecular targets of natural drug substances

Abstract

All creatures – bacteria, plants, animals, humans – have many building blocks in common, down to biochemical structures. That is why natural substances seem to be better able to bind, and bind specifically, to drug targets in man. This is supported, for instance, by a principal component analysis of a large number of combinatorial and natural products and drugs that revealed the greater chemical similarity of the latter two [1]. How about target preferences of natural products in comparison to synthetic drugs? Recently, a comprehensive compilation and analysis of molecular targets of drug substances irrespective of their origin was published [2]. The talk will categorise targets chemically and analyse the nature of drug targets. It will stress the dynamics of drug action because an effective drug target comprises a biochemical system rather than a single molecule. The focus will be on targets of natural compounds that are or were in use as therapeutic agents, and compare this with targets of drugs in general. Differences will be traced to historical, chemical, pharmacological, and social reasons. For 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. 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 function that may be used as antibacterials.