Parasitology

Biography

Biography: Mohammed Tarique

Abstract

Malaria is of one of the major public health problem especially in tropical and subtropical region of the world including India. The disease is caused by the protozoan parasite, Plasmodium species and responsible for more than six million human deaths worldwide. Although some drugs are available for the treatment of malaria but the development of resistance to the currently available drugs is a major concern. Thus there is an urgent need to identify suitable chemotherapeutic targets in order to develop newer class of antimalarials. Recently major components of the DNA mismatch repair like PfMLH and Plasmodium specific UvrD have been identified and characterized. PfUvrD helicase interact with PfMLH and seems crucial for the parasite survival thus can emerge as suitable drug target. Recently we have reported that Plasmodium falciparum contains UvrD, which is absent in the human host and their interplay with MLH is crucial for the modulation of each other’s biochemical activities. PfUvrD knockdown showed that it is required for the parasite during intraerythrocytic development. In this study we focused on the MLH to find some inhibitor molecule of their biochemical activities. In order to find the inhibitor for the biochemical activities of PfMLH, we have screened the various DNA interacting compounds and our data reveal that Etoposide, Nogalamycin, Netropsin, Daunorubicin and ethidium bromide inhibit the ATPase activity of MLH in the in vitro assay. Identified compounds were further in silico-studied and docking result show some crucial amino acid of the ATPase active site. In silico analysis of the binding of Etoposide, Nogalamycin, Netropsin, Daunorubicin and with synthetic PfMLH protein clearly reveals that Asp83 (D-83) of ATPase domain-I is involved in polar interaction with these compounds and may be crucial for ATPase activity. Thus our results suggest that Etoposide, Nogalamycin, Netropsin, Daunorubicin and ethidium bromide are the crucial inhibitors of the ATPase activity of PfMLH. These data from this study can be further utilized to design analogs or novel inhibitors to specifically target the crucial component of MMR machinery i.e. PfMLH proteins. Considering the previous and current finding about PfMLH and PfUvrD, it seems that targeting their interaction and or their biochemical activities may emerge as suitable therapeutic target for the control of malaria.