Synthesis, Structure - Activity Relationships and Biological Studies of Chromenochalcones as Potential Antileishmanial Agents

Abstract

Antileishmanial activities of a library of synthetic chalcone analogues have been examined. Among them, five compounds (11, 14, 16, 17, 22 and 24) exhibited better activity than the marketed drug miltefosine in in vitro studies against intracellular amastigotes form of Leishmania donovani. Three promising compounds 16, 17 and 22 were tested in L. donovani / hamster model. Oral administration of chalcone 16, at a concentration of 100 mg/kg of body weight per day for 5 consecutive days resulted in >84% parasite inhibition at day 7 post-treatment and it retained the activity till day 28. The molecular and immunological studies revealed that compound 16 has a dual nature to act as a direct parasite killing agent and as a host immunostimulant. Pharmacokinetics and serum albumin binding studies also suggest that compound 16 has potential to be a candidate for the treatment of non-healing form of leishmaniasis.