Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov str., 8, Kazan 420088, Russia.
Southern Federal University, Stachki Avenue, 194/2, Rostov-on-Don 344090, Russia.
Molecules. 2019 Aug 25;24(17):3086. doi: 10.3390/molecules24173086.
A library of novel 2-(het)arylpyrrolidine-1-carboxamides were obtained via a modular approach based on the intramolecular cyclization/Mannich-type reaction of -(4,4-diethoxybutyl)ureas. Their anti-cancer activities both in vitro and in vivo were tested. The in vitro activity of some compounds towards M-Hela tumor cell lines was twice that of the reference drug tamoxifen, whereas cytotoxicity towards normal Chang liver cell did not exceed the tamoxifen toxicity. In vivo studies showed that the number of surviving animals on day 60 of observation was up to 83% and increased life span (ILS) was up to 447%. Additionally, some pyrrolidine-1-carboxamides possessing a benzofuroxan moiety obtained were found to effectively suppress bacterial biofilm growth. Thus, these compounds are promising candidates for further development both as anti-cancer and anti-bacterial agents.
通过基于 -(4,4-二乙氧基丁基)脲的分子内环化/Mannich 型反应的模块化方法，获得了一系列新型 2-(杂芳基)吡咯烷-1-甲酰胺。测试了它们在体外和体内的抗癌活性。一些化合物对 M-Hela 肿瘤细胞系的体外活性是参考药物他莫昔芬的两倍，而对正常 Chang 肝细胞的细胞毒性不超过他莫昔芬的毒性。体内研究表明，在观察第 60 天存活的动物数量高达 83%，并增加了寿命（ILS）高达 447%。此外，获得的含有苯并呋喃酮部分的一些吡咯烷-1-甲酰胺被发现能有效抑制细菌生物膜的生长。因此，这些化合物有希望作为抗癌和抗菌剂进一步开发。
