title: Novel 12N-substituted matrinanes as potential anti-coxsackievirus agents.
abstract: A series of novel 12N-substituted matrinane derivatives were synthesized and evaluated for their activities against coxsackievirus type B3 (CVB3) taking compound 1 as the lead. SAR analysis indicated that the introduction of a suitable heteroaromatic ring on the 12N-atom might be beneficial for the activity. Among them, compound 8a exhibited the highest potency against all CVB serotypes as well as CVA16 with IC50values ranging from 2.02μM to 7.41μM, indicating a broad-spectrum anti-coxsackieviruse effect. Furthermore, compound 8a demonstrated a good safety profile in vivo. Thus, we consider 12N-substituted matrinanes to be a promising family of anti-coxsackievirus agents, and compound 8a to be a promising drug candidate in the treatment of various diseases related to coxsackievirus infection.
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: 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: 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.
authors.forename: Xin-Yue
authors.initials: XY
authors.lastname: Cheng
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
authors.forename: Yan-Xiang
authors.initials: YX
authors.lastname: Wang
authors.affiliation: College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China. Electronic address: sufengvip@126.com.
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. Electronic address: songdanqingsdq@hotmail.com.
authors.forename: Dan-Qing
authors.initials: DQ
authors.lastname: Song
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004770:Enterovirus / Q000187:drug effects; D029822:Enterovirus B, Human / Q000187:drug effects; D007928:Lethal Dose 50; D051379:Mice; D013329:Structure-Activity Relationship; D000093842:Matrines
chemical_list: D000470:Alkaloids; D000998:Antiviral Agents; C035933:sophocarpine; D000093842:Matrines
keywords: Broad-spectrum; Coxsakievirus; Druglike; Matrinane; Structure–activity relationship