Designing Promiscuous Drugs? Look at What Nature Made!

Arsenio   M.   Fialho; Tapas   K.   Das Gupta; Ananda   M.   Chakrabarty

Abstract

For the last several years, the drug industry primarily has relied on drugs that target a single gene or enzyme in a pathway involved in disease progression with the idea that such a drug will have minimum side effects and maximal efficacy. Recent observations, however, indicate that a drug that targets multiple genes/enzymes involved in several pathways, thus exhibiting promiscuity, is often more efficacious with less side effects. Thus significant efforts are being made to use our understanding in pharmacogenomics and structural biology to design polypharmacological drugs that are able to act at multiple sites. Recent studies with pathogenic bacteria demonstrate that such bacteria produce water-soluble, low molecular weight redox proteins that appear to act as weapons against various invaders, internal or external, of human body that cause diseases such as cancers, malaria or AIDS. The potential of finding such promiscuous lipophilic bacterial proteins active against multiple diseases may lead in the future to an antibiotic-like industry targeted towards non-prokaryotic agents of human diseases.

Keywords: Azurin, Cancer, Malaria, AIDS, Bacterial pathogenicity, Single and multiple target drugs

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