Synthesis and biological evaluation of fluorinated 3,4-dihydroquinolin-2(1 H)-ones and 2-oxindoles for anti-hepatic fibrosis

氟化3,4-二氢喹啉-2(1H)-酮和2-氧吲哚的合成及抗肝纤维化的生物学评价

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作者:Man Li, Fu-Sheng He, Long-Shan Ji, Ya-Ting Gao, Xin Zhang, Zhuo Yu, Miao Fang, Jie Wu, Yue-Qiu Gao

Abstract

(Z)-4-(Iodomethylene)-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinolin-2(1H)-ones and fluorinated 3,3-disubstituted 2-oxindoles are synthesized and evaluated for anti-hepatic fibrosis. CCK-8 assay indicates that most of the compounds have no obvious cytotoxicity on the human hepatic stellate cells (HSC) cell line. Collagen I and fibrosin expression levels are tested by ELISA, and the results show that several compounds can inhibit the expression of collagen I and fibrosin. Additionally, results from real time-PCR reveal that only one compound can inhibit the expression level of α-SMA, suggesting that this compound can inhibit the activation of the HSC cell line. These studies demonstrate that this compound may be a potential novel drug candidate for anti-hepatic fibrosis (approximately 5-6 lines).

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