title: A novel p-terphenyl derivative inducing cell-cycle arrest and apoptosis in MDA-MB-435 cells through topoisomerase inhibition.
abstract: A novel series of p-terphenyl derivatives (1-4, 1a-4a) was successfully synthesized and their in vitro anticancer activities were evaluated. Compound 1, showing the best antiproliferative activity with IC50<1 μM against MDA-MB-435 cells, was further investigated. Compound 1 brought about a remarkable accumulation of MDA-MB-435 cells in G2/M phase prior to the induction of apoptosis. Further antitumor mechanism study indicated that compound 1, which inhibited the enzyme activity of Topo I and Topo IIα by interfering predominantly with the enzyme, could be topoisomerase suppressors instead of poisons. We conclude that compound 1 represents a novel class of Topo catalytic suppressors for developing new chemotherapeutic agents.
authors: Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan 250012, Shandong, PR China; School of Pharmaceutical Sciences, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong, PR China.
authors: Jin
authors: J
authors: Qiu
authors: Baobing
authors: B
authors: Zhao
authors: Yan
authors: Y
authors: Shen
authors: Wang
authors: W
authors: Chen
authors: Yudao
authors: Y
authors: Ma
authors: Yuemao
authors: Y
authors: Shen
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D013730:Terphenyl Compounds / Q000737:chemistry* / Q000494:pharmacology*; D059003:Topoisomerase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D013730:Terphenyl Compounds; D059003:Topoisomerase Inhibitors
keywords: Apoptosis; Suppressors; Terphenyls; Topoisomerase