Department of Biotechnology and Food Technology, Durban University of Technology, Durban 4001, South Africa.
Chem Biol Drug Des. 2013 Feb;81(2):219-27. doi: 10.1111/cbdd.12065. Epub 2012 Nov 14.
A series of 2-(substituted phenyl/benzyl-amino)-6-(4-chlorophenyl)-5-(methoxycarbonyl)-4-methyl-3,6-dihydropyrimidin-1-ium chlorides 7-13 and 15 was synthesized in their hydrochloride salt form. The title compounds were characterized by FT-IR, NMR ((1)H and (13)C) and elemental analysis. They were evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv, multidrug resistance tuberculosis and extensively drug resistance tuberculosis by agar diffusion method and tested for the cytotoxic action on peripheral blood mononuclear cells by MTT assay. Among all the tested compounds in the series, compounds 7 and 11 emerged as promising antitubercular agents at 16 μg/mL against multidrug resistance tuberculosis and over 64 μg/mL against extensively drug resistance tuberculosis. The conformational features and supramolecular assembly of the promising compounds 7 and 11 were determined by single crystal X-ray study.
一系列 2-(取代苯基/苄基氨基)-6-(4-氯苯基)-5-(甲氧基羰基)-4-甲基-3,6-二氢嘧啶-1-鎓氯化物 7-13 和 15 以盐酸盐的形式合成。标题化合物通过 FT-IR、NMR((1)H 和 (13)C)和元素分析进行了表征。通过琼脂扩散法评估了它们对结核分枝杆菌 H37Rv、耐多药结核分枝杆菌和广泛耐药结核分枝杆菌的体外抗结核活性，并通过 MTT 测定法测试了它们对外周血单个核细胞的细胞毒性作用。在所测试的所有化合物中，化合物 7 和 11 在 16 μg/mL 时对耐多药结核分枝杆菌和超过 64 μg/mL 时对广泛耐药结核分枝杆菌表现出有希望的抗结核作用。通过单晶 X 射线研究确定了有前途的化合物 7 和 11 的构象特征和超分子组装。
