Title:Heat Shock Protein 90 Inhibitors as Broad Spectrum Anti-Infectives
Volume: 19
Issue: 3
Author(s): Ankit K. Rochani, Meetali Singh and Utpal Tatu
Affiliation:
Keywords:
Hsp90 inhibitors, anti-infective, 17-AAG, Plasmodium falciparum Hsp90, malaria, surra, Candida, Giardia, Trypanosoma, molecular chaperone.
Abstract: Combating stress is one of the prime requirements for any organism. For parasitic microbes, stress levels are highest during the
growth inside the host. Their survival depends on their ability to acclimatize and adapt to new environmental conditions. Robust cellular
machinery for stress response is, therefore, both critical and essential especially for pathogenic microorganisms. Microbes have cleverly
exploited stress proteins as virulence factors for pathogenesis in their hosts. Owing to its ability to sense and respond to the stress conditions,
Heat shock protein 90 (Hsp90) is one of the key stress proteins utilized by parasitic microbes. There are growing evidences for the
critical role played by Hsp90 in the growth of pathogenic organisms like Candida, Giardia, Plasmodium, Trypanosoma, and others. This
review, therefore, explores potential of exploiting Hsp90 as a target for the treatment of infectious diseases. This molecular chaperone has
already gained attention as an effective anti-cancer drug target. As a result, a lot of research has been done at laboratory, preclinical and
clinical levels for several Hsp90 inhibitors as potential anti-cancer drugs. In addition, lot of data pertaining to toxicity studies, pharmacokinetics
and pharmacodynamics studies, dosage regime, drug related toxicities, dose limiting toxicities as well as adverse drug reactions
are available for Hsp90 inhibitors. Therefore, repurposing/ repositioning strategies are also being explored for these compounds
which have gone through advanced stage clinical trials. This review presents a comprehensive summary of current status of development
of Hsp90 as a drug target and its inhibitors as candidate anti-infectives. A particular emphasis is laid on the possibility of repositioning
strategies coupled with pharmaceutical solutions required for fulfilling needs for ever growing pharmaceutical infectious disease market.
