title: Design, synthesis, and biological evaluation of benzoselenazole-stilbene hybrids as multi-target-directed anti-cancer agents.
abstract: To identify novel multi-target-directed drug candidates for the treatment of cancer, a series of benzoselenazole-stilbene hybrids were synthesised by combining the pharmacophores of resveratrol and ebselen. The biological assay indicated that all of the hybrids exhibited antiproliferative activities against four human cancer cell lines and demonstrated good TrxR inhibitory activities. The mechanism of cell apoptosis was investigated in G2/M cell cycle arrest induced by compound 6e and the apoptosis of the human liver carcinoma Bel-7402 cell line. The significant increase in intracellular ROS confirmed that compound 6e was capable of causing oxidative stress-induced apoptosis in cancer cells. Our results support the potential of compound 6e as a candidate for further studies examining the development of novel drugs for cancer treatment.
authors.affiliation: Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.affiliation: Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Yueyan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Mao
authors.affiliation: Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. Electronic address: huangl72@mail.sysu.edu.cn.
authors.forename: Ling
authors.initials: L
authors.lastname: Huang
authors.affiliation: Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. Electronic address: lixsh@mail.sysu.edu.cn.
authors.forename: Xingshu
authors.initials: X
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D005434:Flow Cytometry; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016566:Organoselenium Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013267:Stilbenes / Q000737:chemistry*; D054481:Thioredoxin Reductase 1 / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
chemical_list: C000604761:2-(4-(3,4-dimethoxystyryl)phenyl)benzo(d)(1,2)selenazol-3(2H)-one; D000970:Antineoplastic Agents; D016566:Organoselenium Compounds; D013267:Stilbenes; C516124:TXNRD1 protein, human; D054481:Thioredoxin Reductase 1
keywords: Antiproliferative activity; Apoptosis; Benzoselenazole-stilbene hybrids; G(2)/M cell cycle arrest; ROS; TrxR