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Synthesis, structure-activity relationships, and biological studies of chromenochalcones as potential antileishmanial agents. 2014
Rahul Shivahare, and
Venkateswarlu Korthikunta, and
Hardik Chandasana, and
Manish K Suthar, and
Pragati Agnihotri, and
Preeti Vishwakarma, and
Telaprolu K Chaitanya, and
Papireddy Kancharla, and
Tanvir Khaliq, and
Shweta Gupta, and
Rabi Sankar Bhatta, and
J Venkatesh Pratap, and
Jitendra K Saxena, and
Suman Gupta, and
Narender Tadigoppula
Division of Parasitology, CSIR-Central Drug Research Institute , Lucknow 226 031, Uttar Pradesh, India.
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 the intracellular amastigotes form of Leishmania donovani. Three promising compounds, 16, 17, and 22, were tested in a 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 until 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 the potential to be a candidate for the treatment of the nonhealing form of leishmaniasis.
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