Synthesis and Anti-Leishmanial activity of certain Oxabicyclo[3.3.1]nonanone and hexahydrobenzo[de] iso-chromans
Anil Kumar Saikia
Indian Institute of Technology-Guwahati, India
: J Pharm Drug Deliv Res
Abstract
Leishmaniasis is a neglected protozoan infection most prevalent in poor population of tropical countries. It is an etiologic agent of broad infection spectrum from self-healing cutaneous leishmaniasis to a devastating and life claiming viceral leishmaniasis is most common form of the disease in India that is known as kala-azar. Search for successful vaccine against the paracite is still elucive. The main stream of treatment solely relies on chemotherapy. Available chemotherapy against leismaniasis exhibit high toxicity and do not prevent emergence of drug resistance. We have been working on the synthesis of oxygen, nitrogen and sulfur heterocyclic chemistry and their evaluation in bilogical activity. In our computational screening processes for inhibitors against redox enzymes of Leishmania, we have identified a new class of compounds that inhibit trypanbothione synthetase (TryS), an enzyme which catalyses the synthesis of T(SH)2 and trypanothione reductase (TryR). Subsequently these compounds were tested against recombinant TryS and TryR enzymes using experimental methods. Compound 4-(4, 4, 8-trimethyl-7-oxo-3-oxabicyclo [3.3.1] non-2-yl) benzoic acid methyl ester showed the highest anti-leismanial activity among all compounds tested. The in vivo assessment of this compound is also carried out in hamsters and the toxicity was studies using Swiss albino mice. The details will be discussed in the meeting.
Biography
Email: asaikia@iitg.ernet.in
