SQ109的氧杂、硫杂、杂环和碳硼烷类似物：细菌和原生动物细胞生长抑制剂。
Oxa, Thia, Heterocycle, and Carborane Analogues of SQ109: Bacterial and Protozoal Cell Growth Inhibitors.
作者信息
Li Kai, Wang Yang, Yang Gyongseon, Byun Sooyoung, Rao Guodong, Shoen Carolyn, Yang Hongliang, Gulati Anmol, Crick Dean C, Cynamon Michael, Huang Guozhong, Docampo Roberto, No Joo Hwan, Oldfield Eric
机构信息
Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, IL 61801.
Leishmania Research Laboratory, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do, Republic of Korea, 463-400.
出版信息
ACS Infect Dis. 2015 May 8;1(5):215-221. doi: 10.1021/acsinfecdis.5b00026.
Abstract
We synthesized a library of 48 analogs of the cell growth inhibitor SQ109 in which the ethylene diamine linker was replaced by oxa-, thia- or heterocyclic species, and in some cases, the adamantyl group was replaced by a 1,2-carborane or the N-geranyl group by another hydrophobic species. Compounds were tested against (H37Rv and/or Erdman), , , , , and two human cell lines (human embryonic kidney, HEK293T, and the hepatocellular carcinoma, HepG2). Most potent activity was found against , the causative agent of human African trypanosomiasis, and involved targeting of the mitochondrial membrane potential with 15 SQ109 analogs being more active than was SQ109 in cell growth inhibition, having IC values as low as 12 nM (5.5 ng/mL) and a selectivity index of ~300.
摘要
我们合成了48种细胞生长抑制剂SQ109的类似物库，其中乙二胺连接基被氧杂、硫杂或杂环物种取代，在某些情况下，金刚烷基被1,2-碳硼烷取代，或N-香叶基被另一种疏水物种取代。对化合物进行了针对（H37Rv和/或Erdman）、、、、、以及两种人类细胞系（人胚肾，HEK293T，和肝癌细胞，HepG2）的测试。发现对人类非洲锥虫病病原体具有最强活性，并且15种SQ109类似物通过靶向线粒体膜电位在细胞生长抑制方面比SQ109更具活性，IC值低至12 nM（5.5 ng/mL），选择性指数约为300。
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