European Journal of Medicinal Chemistry p. 282 - 292 (2017)
Update date:2022-08-25
Topics:
Lee, Jin-Ching
Tseng, Chin-Kai
Lin, Chun-Kuang
Tseng, Chih-Hua
A number of diarylpyrazolylquinoline derivatives were synthesized and evaluated for their anti-dengue virus (DENV) activity. Among them, 6-fluoro-2-(1-(4-fluorophenyl)-3- (4-methoxyphenyl)-1H-pyrazol-5-yl)quinoline (11c), 2-[1,3-bis(4-methoxyphenyl)-1H-pyrazol- 5-yl]-6-fluoroquinoline (12c), and 4-[5-(6-fluoroquinolin-2-yl)-3-(4-methoxyphenyl)-1H-pyrazol- 1-yl]benzenesulfonamide (13c) exhibited approximately 10-folds more active anti-DENV-2 activity (IC50 of 1.36, 1.09 and 0.81 μM, respectively) than that of ribavirin (IC50 = 12.61 μM). Compound 13c was also potent inhibited other sero-types of DENV. It reduced DENV replication in both viral protein and mRNA levels, and no significant cell cytotoxicity was detected, with greater than 50% viability of Huh-7-DV-Fluc cells at a concentration of 200 μM. Furthermore, compound 13c can effectively protect mice from DENV infection by reducing disease symptoms and mortality of DENV-infected mice. It represents a potential antiviral agent to block DENV replication in vitro and in vivo. Structural optimization of the initial lead compound, 13c, and the detailed molecular mechanism of action are ongoing.
View MoreNanjing distinctions Medical Technology Co., Ltd.
Contact:+86-15996203785 13914714059
Address:nanjing,jiangsu , China
Jiangsu Zenji Pharmaceuticals LTD
Contact:+86-025-83172562; +1-224-888-1133(USA)
Address:No.5 Xinmofan Road
jintan yufan Medicine Raw materials Co.,Ltd.
Contact:86-519-82808282
Address:6th,Jincheng Huangzhuang
website:http://www.lonwinchem.com
Contact:Tel: 86-21-59858395
Address:No#966,Huaxu Road,Shanghai 201702,P.R.China
Guangzhou PI & PI Biotech Inc. Ltd.
Contact:+86-20-81716320
Address:Suite 501,198 Kaiyuan Ave.,Science City, Guangzhou,China
Doi:10.1039/c3cc49530b
(2014)Doi:10.1016/S0040-4039(00)99736-3
(1970)Doi:10.3987/COM-93-6570
(1994)Doi:10.1021/jo00144a018
(1982)Doi:10.1135/cccc19831891
(1983)Doi:10.1021/acs.jmedchem.7b00076
(2017)