Chapter

Heat Shock Proteins of Malaria

pp 189-205

Date:

Heat Shock Proteins as Targets for Novel Anti-Malarial Drugs

  • Manish GroverAffiliated withDepartment of Biochemistry, Indian Institute of Science
  • , Shweta ChaubeyAffiliated withDepartment of Biochemistry, Indian Institute of Science
  • , Utpal TatuAffiliated withDepartment of Biochemistry, Indian Institute of Science Email author 

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Abstract

Molecular chaperones or heat shock proteins are involved in diverse biological processes and play an important role in maintaining cellular homeostasis. Thus, inhibiting their function can be detrimental to cell survival. It has been well established that elaborate involvement of heat shock proteins is required during the process of malaria pathogenesis. Hence, heat shock proteins serve as potential drug targets against malaria. The emergence of drug resistance in Plasmodium falciparum against existing anti-malarial drugs has created a pressing need for the identification of novel drug targets. Multiple strategies have been undertaken in this regard which involve target based drug discovery, identifying novel anti-malarial natural compounds, chemically modifying existing drugs or repurposing drugs used for other diseases. This chapter provides a comprehensive overview of the inhibitors of Hsp90 and Hsp70-40 molecular chaperone system tested for efficacy in Plasmodium falciparum. These compounds belong to diverse chemical families and are of both natural and synthetic origin. Naturally occurring napthoquinones and synthetic pyrimidinones target PfHsp70 function while geldanamycin, acrisorcin, APPA and harmine are natural compounds that inhibit PfHsp90 function. Some of these compounds like geldanamycin and its derivative 17-AAG have been also tested in the mouse model of malaria and have been found to be very effective. Overall, heat shock protein inhibitors not only provide us with a new avenue to tackle malaria but also shed light on novel features of parasite’s biology.

Keywords

Hsp90 Hsp70 Anti-malarial Geldanamycin Pyrimidinone Napthoquinone