烷二酰胺连接的双苯甲脒的合成及构效关系研究，具有抗锥虫和抗肺囊虫活性。
Synthesis and SAR of alkanediamide-linked bisbenzamidines with anti-trypanosomal and anti-pneumocystis activity.
机构信息
Xavier University of Louisiana, College of Pharmacy, 1 Drexel Drive, New Orleans, LA 70125, USA.
出版信息
Bioorg Med Chem Lett. 2009 Oct 15;19(20):5884-6. doi: 10.1016/j.bmcl.2009.08.073. Epub 2009 Aug 23.
Abstract
A series of alkanediamide-linked bisbenzamidines was synthesized and tested in vitro against a drug-sensitive strain of Trypanosoma brucei brucei, a drug-resistant strain of Trypanosoma brucei rhodesiense and Pneumocystiscarinii. Bisbenzamidines linked with longer alkanediamide chains were potent inhibitors of both strains of T. brucei. However, bisbenzamidines linked with shorter alkanediamide chains were the most potent compounds against P. carinii. N,N'-Bis[4-(aminoiminomethyl)phenyl] hexanediamide, 4 displayed potent inhibition (IC50=2-3 nM) against T. brucei and P. carinii, and was non-cytotoxic in the A549 human lung carcinoma cell line. The inhibitory bioactivity was significantly reduced when the amidine groups in 4 were moved from the para to the meta positions or replaced with amides.
摘要
合成了一系列烷二酰胺连接的双苯甲脒，并在体外对敏感型布氏锥虫布鲁斯株、耐药型布氏锥虫罗得西亚株和卡氏肺孢子虫进行了测试。与较长的烷二酰胺链连接的双苯甲脒对两种布氏锥虫均有很强的抑制作用。然而，与较短的烷二酰胺链连接的双苯甲脒是针对卡氏肺孢子虫最有效的化合物。N,N'-双[4-(氨基亚氨基甲基)苯基]己二脒 4 对布氏锥虫和卡氏肺孢子虫表现出很强的抑制作用（IC50=2-3 nM），并且在人肺癌 A549 细胞系中无细胞毒性。当 4 中的脒基从对位移动到间位或被酰胺取代时，抑制生物活性显著降低。
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