Departamento de Química, Instituto de Química, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Bioorg Med Chem Lett. 2012 Oct 15;22(20):6486-9. doi: 10.1016/j.bmcl.2012.08.048. Epub 2012 Aug 21.
TB is a global public health emergency in which new drugs are desperately needed. Herein we report on the synthesis of a diverse panel of 41 aryl allylic azides, thiocyanates, isothiouronium salts, and N,N'-diacetylisothioureas that were evaluated for their in vitro activity against replicating and non-replicating Mycobacterium tuberculosis (Mtb) H(37)Rv and toxicity to VERO cells. We found a selective group of new and promising compounds having good (micromolar) to excellent (sub-micromolar) potency against replicating Mtb H(37)Rv. Allylic thiocyanates bearing halophenyl (halo=2-Br, 4-Br, 4-Cl, 4-F), 4-methylphenyl and 2-naphthyl moieties were the most active as antitubercular agents. In particular, the 2-bromophenyl-substituted thiocyanate showed MIC=0.25 μM against replicating Mtb, MIC=8.0 μM against non-replicating Mtb and IC(50)=32 μM in the VERO cellular toxicity assay.
结核病是一种全球公共卫生紧急情况，急需新的药物。在此，我们报告了合成了一组多样化的 41 种芳基烯丙基叠氮化物、硫氰酸盐、异硫脲盐和 N,N'-二乙酰基异硫脲，评估了它们对复制和非复制结核分枝杆菌（Mtb）H（37）Rv 的体外活性和对 VERO 细胞的毒性。我们发现了一组新的有希望的化合物，它们对复制的 Mtb H（37）Rv 具有良好（微摩尔级）至优异（亚微摩尔级）的活性。带有卤代苯基（卤代=2-Br、4-Br、4-Cl、4-F）、4-甲基苯基和 2-萘基部分的烯丙基硫氰酸盐是最有效的抗结核药物。特别是，2-溴代苯基取代的硫氰酸盐对复制的 Mtb 的 MIC=0.25 μM，对非复制的 Mtb 的 MIC=8.0 μM，在 VERO 细胞毒性测定中的 IC（50）=32 μM。
