Study carried out by UoH and NIPER, Hyderabad
Visceral leishmaniasis, also called as ‘Kala azar’, is an infectious disease caused by the protozoan parasite Leishmania donovani and transmitted by the bite of infected sand flies. It is considered as a second-largest parasitic killer with nearly one million new cases and about 30,000 deaths reported annually in over 80 countries around the globe. More than 90% of the cases occur in countries such as Bangladesh, Brazil, Ethiopia, India, South Sudan and Sudan. It is a serious public health problem in India and has been an endemic since ancient times, particularly in Bihar state. Absence of effective vaccine, increasing co-infections with HIV, toxicity and emerging resistance against current line of antileishmanials are the limiting factors to cure the disease. Hence, there is an urgent need to search for novel chemotherapeutic options for the treatment of this tropical neglected disease.
The research group of Dr. Insaf Ahmed Qureshi at School of Life Sciences, University of Hyderabad (UoH) in collaboration with NIPER, Hyderabad have shown that methionine aminopeptidase 1, a crucial enzyme for the survival of leishmanial parasite Leishmania donovani (LdMetAP1) can be used as a target for developing new therapy for treating leishmanial diseases. They screened several newly synthesized quinoline carbaldehyde derivatives using inhibition assays and identified two novel and specific inhibitors HQ14 and HQ15 that inhibit the activity of LdMetAP1. Both leads bind LdMetAP1 with high affinity and possess druglikeness. Remarkably, these inhibitors do not affect the human counterpart (HsMetAP1) of the drug target, negating possible side effects posed by them. In addition, the study also highlights monumental difference in binding modes of human and parasitic methionine aminopeptidase 1 with the inhibitors. The present inhibition studies on leishmanial parasite might provide a road map for proceeding of these inhibitors towards clinical trials to fight against this fatal disease. Results of the research have been published in European Journal of Medicinal Chemistry, a reputed journal in the field of medicinal chemistry.