Synthesis, Structure鈥揂ctivity Relationships, and Biological Studies of Chromenochalcones as Potential Antileishmanial Agents

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• 作者：Rahul Shivahare ; Venkateswarlu Korthikunta ; Hardik Chandasana ; Manish K. Suthar ; Pragati Agnihotri ; Preeti Vishwakarma ; Telaprolu K. Chaitanya ; Papireddy Kancharla ; Tanvir Khaliq ; Shweta Gupta ; Rabi Sankar Bhatta ; J. Venkatesh Pratap ; Jitendra K. Saxena ; Suman Gupta ; Narender Tadigoppula
• 刊名：Journal of Medicinal Chemistry
• 出版年：2014
• 出版时间：April 24, 2014
• 年：2014
• 卷：57
• 期：8
• 页码：3342-3357
• 全文大小：777K
• 年卷期：v.57,no.8(April 24, 2014)
• ISSN：1520-4804

文摘

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.