title: Structure-activity relationships study of 6-chloro-4-(2-chlorophenyl)-3-(2-hydroxyethyl) quinolin-2(1H)-one derivatives as novel non-nucleoside anti-hepatitis B virus agents.
abstract: A series of novel 6-chloro-4-(2-chlorophenyl)-3-(2-hydroxyethyl) quinolin-2(1H)-one derivatives were synthesized and evaluated for anti-hepatitis B virus (anti-HBV) activities in vitro to explore their structure-activity relationships (SARs). Most of the synthesized compounds possessed potent anti-HBV activity, of which the promising compound 44 exhibited significantly inhibitory potency against the secretion of hepatitis surface antigen (HBsAg) (IC(50) = 0.010 mM, SI > 135), hepatitis e antigen (HBeAg) (IC(50) = 0.026 mM, SI > 51) and the replication of HBV DNA (IC(50) = 0.045 mM). Preliminary mechanism study suggested compound 44 could mainly enhance the transcript activity of HBV ENI (enhancer I), EN-II (enhancer II).
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, PR China.
authors.forename: Rui-Hua
authors.initials: RH
authors.lastname: Guo
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yun-Bao
authors.initials: YB
authors.lastname: Ma
authors.forename: Jie
authors.initials: J
authors.lastname: Luo
authors.forename: Chang-An
authors.initials: CA
authors.lastname: Geng
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Wang
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Jiang
authors.forename: Ji-Jun
authors.initials: JJ
authors.lastname: Chen
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects; D004279:DNA, Viral / Q000096:biosynthesis; D004742:Enhancer Elements, Genetic / Q000235:genetics; D056945:Hep G2 Cells; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006513:Hepatitis B e Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D015363:Quinolones