Division of Parasitology, CSIR-Central Drug Research Institute , Lucknow 226 031, Uttar Pradesh, India.
J Med Chem. 2014 Apr 24;57(8):3342-57. doi: 10.1021/jm401893j. Epub 2014 Apr 2.
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.
已经研究了一系列合成查耳酮类似物的抗利什曼原虫活性。在这些化合物中，有 5 种（11、14、16、17、22 和 24）在体外试验中对利什曼原虫内阿米巴形式的活性优于市售药物米替福新。三种有前途的化合物 16、17 和 22 在利什曼原虫/仓鼠模型中进行了测试。在连续 5 天每天口服 100mg/kg 体重的查耳酮 16，在治疗后第 7 天可抑制超过 84%的寄生虫，并且在第 28 天仍保持活性。分子和免疫研究表明，化合物 16 具有双重性质，既能直接杀死寄生虫，又能刺激宿主免疫。药代动力学和血清白蛋白结合研究也表明，化合物 16 有潜力成为治疗非愈合型利什曼病的候选药物。
