Department of Pharmaceutical Chemistry, Telangana University, Dichpally, Nizamabad, 503322, India.
Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Hajipur, 844102, India.
Chem Biodivers. 2021 Jul;18(7):e2100105. doi: 10.1002/cbdv.202100105. Epub 2021 Jun 4.
We have developed a new series of simple biaryl piperidine derivatives (11-19) based on biaryl naphthylisoquinoline alkaloid Ealamine-A. The target compounds were synthesized, analyzed by spectral data, and evaluated for antileishmanial activity against Leishmania donovani strain Ag83 by MTT assay. The compounds have shown the best to moderate antileishmanial activity. The 5'-fluoro-2'-methoxyphenyl derivative 14 and 3',5'-difluorophenyl derivative 16 have inhibited the promastigotes by 86 % and 85 % after 24 h and 92 % and 91 % after 48 h incubation, respectively, at 400 μM concentration. The % inhibition was lower with the lowering of the concentration and increased with the incubation time. Compounds 12, 15, and 18 have solubility issues and proved to be less active than the rest of the compounds. Molecular docking studies were performed on selective active compounds and the results indicate that these compounds may act by binding to the Leishmanolysin and the docking scores are in good correlation with the antileishmanial activity. These results provide an initial insight into the design of new therapeutics for neglected tropical diseases.
我们基于双芳基萘基异喹啉生物碱 Ealamine-A 开发了一系列新型简单的双芳基哌啶衍生物（11-19）。目标化合物通过光谱数据分析进行了合成和分析，并通过 MTT 测定法评估了对利什曼原虫 Donovan 株 Ag83 的抗利什曼原虫活性。这些化合物表现出最佳至中等抗利什曼原虫活性。5'-氟-2'-甲氧基苯基衍生物 14 和 3'，5'-二氟苯基衍生物 16 在 400μM 浓度下分别孵育 24 小时后抑制前鞭毛体 86%和 85%，孵育 48 小时后抑制 92%和 91%。随着浓度的降低，抑制率降低，随着孵育时间的延长，抑制率增加。化合物 12、15 和 18 存在溶解度问题，证明其活性低于其他化合物。对选择性活性化合物进行了分子对接研究，结果表明这些化合物可能通过与利什曼素结合发挥作用，并且对接分数与抗利什曼原虫活性具有良好的相关性。这些结果为设计新的治疗方法治疗被忽视的热带病提供了初步的见解。
