title: Structure-activity relationship of N-benzenesulfonyl matrinic acid derivatives as a novel class of coxsackievirus B3 inhibitors.
abstract: A novel series of N-benzenesulfonyl matrinic amine/amide and matrinic methyl ether analogues were designed, synthesized and evaluated for their in vitro anti-coxsackievirus B3 (CVB3) activities. The structure-activity relationship (SAR) studies revealed that introduction of a suitable amide substituent on position 4' could greatly enhance the antivirus potency. Compared to the lead compounds, the newly synthesized matrinic amide derivatives 21c-d and 21j exhibited stronger anti-CVB3 activities with lower micromolar IC50 from 2.5 μM to 2.7 μM, and better therapeutic properties with improved selectivity index (SI) from 63 to 67. The SAR results provided powerful information for further strategic optimization, and these top compounds were selected for the next evaluation as novel enterovirus inhibitors.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China; College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China.
authors.forename: Sheng-Gang
authors.initials: SG
authors.lastname: Wang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
authors.forename: Lan-Ying
authors.initials: LY
authors.lastname: Kong
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
authors.forename: Ying-Hong
authors.initials: YH
authors.lastname: Li
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
authors.forename: Xin-Yue
authors.initials: XY
authors.lastname: Cheng
authors.affiliation: College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Su
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Tang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
authors.forename: Chong-Wen
authors.initials: CW
authors.lastname: Bi
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Jiang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China. Electronic address: yuhuanlibj@126.com.
authors.forename: Yu-Huan
authors.initials: YH
authors.lastname: Li
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China. Electronic address: songdanqingsdq@hotmail.com.
authors.forename: Dan-Qing
authors.initials: DQ
authors.lastname: Song
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D002522:Chlorocebus aethiops; D004353:Drug Evaluation, Preclinical / Q000379:methods; D029822:Enterovirus B, Human / Q000187:drug effects* / Q000472:pathogenicity; D013329:Structure-Activity Relationship; D014709:Vero Cells / Q000187:drug effects / Q000821:virology
chemical_list: D000998:Antiviral Agents
keywords: Coxsackievirus B3; Enterovirus; Matrinic amide; Matrinic amine; Structure–activity relationship