title: Semisynthesis of (-)-Rutamarin Derivatives and Their Inhibitory Activity on Epstein-Barr Virus Lytic Replication.
abstract: (+)-Rutamarin inhibits EBV lytic DNA replication with an IC50of 7.0 μM. (-)-Chalepin, a (-)-rutamarin derivative, was isolated from the whole plant of Ruta graveolens and used as a precursor of (-)-rutamarin. Altogether, 28 (-)-rutamarin derivatives were synthesized starting from (-)-chalepin. Of these, 16 compounds (2a-e, 3b-e, 3g, 4f, 4k, 4m-p) were found to be more potent against EBV lytic DNA replication than (-)-chalepin. Compounds 4m, 4n, and 4p exhibited IC50values of 1.5, 0.32, and 0.83 μM and showed selectivity index values (SI) of 801, 211, and >120, respectively. Thus, compounds 4m, 4n, and 4p are considered promising leads for further laboratory investigation.
authors.affiliation: Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou 510006, People's Republic of China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Lin
authors.affiliation: The Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, Guangdong 510080, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou 510006, People's Republic of China.
authors.forename: Qiong
authors.identifier: 0000-0001-6011-3697
authors.initials: Q
authors.lastname: Gu
authors.affiliation: Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou 510006, People's Republic of China.
authors.forename: Hongao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou 510006, People's Republic of China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Jiang
authors.affiliation: The Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, Guangdong 510080, People's Republic of China.
authors.forename: Jiayuan
authors.initials: J
authors.lastname: Hu
authors.affiliation: Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology , Guangzhou 510080, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, Guangdong 510080, People's Republic of China.|Department of Microbiology, School of Dental Medicine, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou 510006, People's Republic of China.
authors.forename: Jun
authors.identifier: 0000-0002-1075-0337
authors.initials: J
authors.lastname: Xu
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000302:isolation & purification* / Q000494:pharmacology*; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000302:isolation & purification* / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects*; D011564:Furocoumarins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004854:Herpesvirus 4, Human / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D032105:Ruta / Q000737:chemistry*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D001578:Benzopyrans; D011564:Furocoumarins; C031533:chalepin; C022850:rutamarin