Discovery and optimization of 2-(trifluoromethyl)benzimidazole derivatives as novel ferroptosis inducers in vitro and in vivo

Autor:	Yuying Fang, Qingyun Tan, Huihao Zhou, Jun Xu, Qiong Gu
Rok vydání:	2023
Předmět:	Pharmacology Antinematodal Agents Liver Neoplasms Organic Chemistry Drug Discovery Humans Ferroptosis Glutamic Acid Benzimidazoles General Medicine
Zdroj:	European Journal of Medicinal Chemistry. 245:114905
ISSN:	0223-5234
DOI:	10.1016/j.ejmech.2022.114905
Popis:	Ferroptosis is implicated in diverse human diseases. Ferroptosis inducers hold great potential for cancer therapy. The existing ferroptosis inducers, however, lack structural diversity, and only a few of them are suitable for in vivo applications. Herein, by phenotypic screenings, we discovered a new ferroptosis inducer FA-S, a 2-(trifluoromethyl)benzimidazole derivative, from which a series of its analogs were designed and synthesized to improve the activity. This produced the most potent compound FA16 with single-digit micromolar activity of ferroptosis induction and satisfactory metabolic stability. Further studies demonstrated that FA16 induced ferroptosis by inhibiting cystine/glutamate antiporter (system X
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ecfb88103275577214c49cbdf75b2b23 https://doi.org/10.1016/j.ejmech.2022.114905 Zobrazit plný text záznamu Full Text from ScienceDirect