title: Anti-HBV and cytotoxic activities of pyranocoumarin derivatives.
abstract: Four natural pyranocoumarins clausenidin (1), nordentatin (2), clausarin (3), and xanthoxyletin (4) were isolated from the medicinal plant Clausena excavata. Recently, we found that 1 and 2 suppressed hepatitis B virus surface antigen in HepA2 cells, and in addition, 1-3 showed cytotoxic activity against four human cancer cell lines (A549, MCF7, KB, and KB-VIN). To explore the SAR of 1-4, 17 pyranocoumarin analogues (5-21) were designed and synthesized. Among these analogues, 5 and 10 were the most potent against hepatitis B virus with EC(50) values of 1.14 and 1.34microM, respectively. The most interesting result in the cytotoxicity assay was the significant activity of 1, 5, and 6 against the multi-drug resistant cell line, KB-VIN, without activity against the KB cell line. These data suggest that these three compounds could be useful hits for developing MDR-inverse drugs.
authors.affiliation: Department of Chemistry, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chung-Ren
authors.initials: CR
authors.lastname: Su
authors.forename: Sheau Farn
authors.initials: SF
authors.lastname: Yeh
authors.forename: Chih Miem
authors.initials: CM
authors.lastname: Liu
authors.forename: Amooru G
authors.initials: AG
authors.lastname: Damu
authors.forename: Tsung-Hsiao
authors.initials: TH
authors.lastname: Kuo
authors.forename: Po-Cheng
authors.initials: PC
authors.lastname: Chiang
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Bastow
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
authors.forename: Tian-Shung
authors.initials: TS
authors.lastname: Wu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D045744:Cell Line, Tumor; D054700:Clausena / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D006515:Hepatitis B virus / Q000187:drug effects*; D006801:Humans; D010946:Plants, Medicinal / Q000737:chemistry; D039681:Pyranocoumarins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D039681:Pyranocoumarins