title: Inhibition of glutathione S-transferase M1 by new gabosine analogues is essential for overcoming cisplatin resistance in lung cancer cells.
abstract: A new class of human GST inhibitors has been identified via rational design approach; we report their discovery, synthesis, inhibitory activity, and synergetic effect in combination with cisplatin against A549 lung cancer cell line. The results of this effort show that the lead 4-O-decyl-gabosine D (24) has optimum synergetic effect in A549 human lung adenocarcinoma epithelial cell and that this activity involves inhibition of glutathione S-transferase M1, apparently consistent with siRNA-mediated knockdown of GSTM1 gene.
authors.affiliation: Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Chie-Hong
authors.initials: CH
authors.lastname: Wang
authors.forename: Ho T
authors.initials: HT
authors.lastname: Wu
authors.forename: Hau M
authors.initials: HM
authors.lastname: Cheng
authors.forename: Tien-Jui
authors.initials: TJ
authors.lastname: Yen
authors.forename: I-Hsuan
authors.initials: IH
authors.lastname: Lu
authors.forename: Hui Chuan
authors.initials: HC
authors.lastname: Chang
authors.forename: Shu-Chuan
authors.initials: SC
authors.lastname: Jao
authors.forename: Tony K M
authors.initials: TK
authors.lastname: Shing
authors.forename: Wen-Shan
authors.initials: WS
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D003512:Cyclohexanones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008175:Lung Neoplasms; D034741:RNA, Small Interfering / Q000235:genetics; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin; D003512:Cyclohexanones; D005982:Glutathione Transferase; D007527:Isoenzymes; D034741:RNA, Small Interfering; C570540:4-O-decyl-gabosine D; C547937:gabosine D