烯丙基硫氰酸酯类作为一类新型抗结核药物。
Allylic thiocyanates as a new class of antitubercular agents.
机构信息
Departamento de Química, Instituto de Química, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
出版信息
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。
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