title: Synthesis, structure-activity relationship and biological evaluation of novel N-substituted matrinic acid derivatives as host heat-stress cognate 70 (Hsc70) down-regulators.
abstract: Oxymatrine (1) is a natural anti-hepatitis B virus (HBV) drug that down-regulates host heat-stress cognate 70 (Hsc70) expression through a mechanism different from that of nucleosides. Taking Hsc70 as a target against HBV, 26 novel N-substituted matrinic acid analogs were designed, synthesized and evaluated for their regulation of Hsc70 mRNA expression with 1 as the lead. The SAR analysis revealed that (i) the carboxyl group at the 11-position was required for activity; (ii) introducing of a substituent on the nitrogen atom at the 12-position of 3, especially substituted benzyl, might significantly improve the activity. Among these analogs, compound 9p possessing N-p-methoxylbenzyl afforded an increased anti-HBV effect in comparison with 1. We consider 9p a promising anti-HBV candidate.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Na-Na
authors.initials: NN
authors.lastname: Du
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.forename: Yan-Xin
authors.initials: YX
authors.lastname: Liu
authors.forename: Chun-Xin
authors.initials: CX
authors.lastname: Li
authors.forename: Zong-Gen
authors.initials: ZG
authors.lastname: Peng
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Gao
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Jiang
authors.forename: Dan-Qing
authors.initials: DQ
authors.lastname: Song
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002087:Butyrates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D050883:HSC70 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016174:Hepacivirus / Q000187:drug effects; D006515:Hepatitis B virus / Q000187:drug effects; D008968:Molecular Conformation; D011807:Quinolizines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D002087:Butyrates; D050883:HSC70 Heat-Shock Proteins; D011807:Quinolizines; D012333:RNA, Messenger