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Synthesis of Novel 2-(Het)arylpyrrolidine Derivatives and Evaluation of Their Anticancer and Anti-Biofilm Activity. 2019
Andrey Smolobochkin, and
Almir Gazizov, and
Marina Sazykina, and
Nurgali Akylbekov, and
Elena Chugunova, and
Ivan Sazykin, and
Anastasiya Gildebrant, and
Julia Voronina, and
Alexander Burilov, and
Shorena Karchava, and
Maria Klimova, and
Alexandra Voloshina, and
Anastasia Sapunova, and
Elena Klimanova, and
Tatyana Sashenkova, and
Ugulzhan Allayarova, and
Anastasiya Balakina, and
Denis Mishchenko
Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov str., 8, Kazan 420088, Russia.
A library of novel 2-(het)arylpyrrolidine-1-carboxamides were obtained via a modular approach based on the intramolecular cyclization/Mannich-type reaction of N-(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.
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