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

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

doi:10.1039/d0ra09430g

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

RSC Adv. 2021 Feb 3;11(11):5923-5927. doi: 10.1039/d0ra09430g. eCollection 2021 Feb 2.

Authors

Man Li¹, Fu-Sheng He², Long-Shan Ji¹, Ya-Ting Gao¹, Xin Zhang¹, Zhuo Yu³, Miao Fang¹, Jie Wu^{2

4

5}, Yue-Qiu Gao^{1

3}

Affiliations

¹ Laboratory of Cellular Immunity, Institute of Clinical Immunology, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shuguang Hospital, Affiliated to Shanghai University of Traditional Chinese Medicine 528 ZhangHeng Road Shanghai 201203 China gaoyueqiu@hotmail.com.
² School of Pharmaceutical and Materials Engineering, Taizhou University 1139 Shifu Avenue Taizhou 31800 China jie_wu@fudan.edu.cn.
³ Department of Hepatology, Shuguang Hospital, Affiliated to Shanghai University of Traditional Chinese Medicine 528 ZhangHeng Road Shanghai 201203 China.
⁴ State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Scinences 354 Fenglin Road Shanghai 200032 China.
⁵ School of Chemistry and Chemical Engineering, Henan Normal University China.

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).