title: Synthesis, antiproliferative activities and in vitro biological evaluation of novel benzofuransulfonamide derivatives.
abstract: In a cell-based screen of novel antiproliferative agents, the hit compound 1a, which bears a benzofuransulfonamide scaffold, exhibited broad-spectrum antiproliferative activities against a panel of tumor cell lines. The promising in vitro antiproliferative activity and structural novelty of 1a prompted us to investigate the synthesis of five analogs of 1a and test their antiproliferative activities. The most potent analogue, 1h, exhibited enhanced antiproliferative activities compared with the parent 1a, and exhibited an IC(50) value against NCI-H460 cells of 4.13 μM compared with 4.52 μM for the positive control cisplatin. Flow cytometric analysis revealed that 1h induces significant levels of apoptosis in NCI-H460 cells in vitro at low micromolar concentrations. These results suggest that 1a and analogs based on its benzofuransulfonamide scaffold may constitute a novel class of antiproliferative agents, which deserve further study.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medicinal School, Sichuan University, Chengdu 610041, Sichuan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Hua
authors.initials: H
authors.lastname: Lei
authors.forename: Cheng-Gen
authors.initials: CG
authors.lastname: Mi
authors.forename: Huan
authors.initials: H
authors.lastname: Liu
authors.forename: Tian
authors.initials: T
authors.lastname: Zhou
authors.forename: Ying-Lan
authors.initials: YL
authors.lastname: Zhao
authors.forename: Xiao-Yun
authors.initials: XY
authors.lastname: Lai
authors.forename: Zi-Cheng
authors.initials: ZC
authors.lastname: Li
authors.forename: Hang
authors.initials: H
authors.lastname: Song
authors.forename: Wen-Cai
authors.initials: WC
authors.lastname: Huang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001572:Benzofurans; D013449:Sulfonamides