合成及评估新型三氮唑基喹啉衍生物作为潜在的抗利什曼原虫药物。
Synthesis and evaluation of novel triazolyl quinoline derivatives as potential antileishmanial agents.
机构信息
Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram extension, Sitapur Road, Lucknow, 226031, India.
Division of Biochemistry, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram extension, Sitapur Road, Lucknow, 226031, India.
出版信息
Eur J Med Chem. 2018 Jun 25;154:172-181. doi: 10.1016/j.ejmech.2018.05.014. Epub 2018 May 12.
The high potential of quinoline containing natural products and their derivatives in medicinal chemistry led us to discover novel series of 25 compounds for the development of new antileishmanial agents. A series of triazolyl 2-methyl-4-phenylquinoline-3-carboxylate derivatives has been synthesized via click chemistry inspired molecular hybridization approach and evaluated against Leishmania donovani. Most of the screened derivatives exhibited significant in vitro anti-leishmanial activity against promastigote (IC ranging from 2.43 to 45.75 μM) and intracellular amastigotes (IC ranging from 7.06 to 34.9 μM) than the control, miltefosine (IC = 8.4 μM), with less cytotoxicity in comparison to the standard drugs. Overall results revealed that prototype signify a new structural lead for antileishmanial chemotherapy.
含喹啉的天然产物及其衍生物在药物化学中的巨大潜力促使我们发现了一系列用于开发新型抗利什曼原虫药物的 25 种化合物。通过点击化学启发的分子杂交方法合成了一系列三唑基 2-甲基-4-苯基喹啉-3-羧酸酯衍生物，并对其进行了抗利什曼原虫的筛选。大多数筛选出的衍生物对前鞭毛体（IC 范围为 2.43 至 45.75μM）和内阿米巴体（IC 范围为 7.06 至 34.9μM）均表现出显著的体外抗利什曼原虫活性，优于对照药物米替福新（IC=8.4μM），且与标准药物相比细胞毒性更低。总体结果表明，该原型化合物为抗利什曼原虫化疗提供了新的结构先导。
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