title: Novel 2-substituted quinolin-4-yl-benzenesulfonate derivatives: synthesis, antiproliferative activity, and inhibition of cellular tubulin polymerization.
abstract: A series of 2-substituted quinolin-4-yl-benzenesulfonate derivatives were synthesized for the purpose of evaluating antiproliferative activity. Structure-activity relationships of the newly synthesized compounds against human lymphoblastic leukemia and various solid tumor cell growths in culture are discussed. Of these derivatives, 2-phenyl-6-pyrrolidinyl-4-quinoline sulfonate analogues 10 f, 10 g, and 10 k, and 4'-nitrophenyl sulfonate 10 m exhibit superior cytotoxicity over other sulfonates. The antiproliferative activities of these compounds correlate well with their abilities to induce mitotic arrest and apoptosis. Mechanistic studies indicate that they target the vinblastine binding site of tubulin and inhibit cellular tubulin polymerization. Hence, these compounds induce the formation of aberrant mitotic spindles and mitotic arrest, resulting in intensive apoptosis. The tested compounds were shown to be poor substrates for membrane multidrug resistance transporters. The present studies suggest that these newly synthesized compounds are promising tubulin polymerization inhibitors and are worthy of further investigation as antitumor agents.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kakadiya
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Wu
authors.forename: Huajin
authors.initials: H
authors.lastname: Dong
authors.forename: Hsiao-Hui
authors.initials: HH
authors.lastname: Kuo
authors.forename: Ling-Huei
authors.initials: LH
authors.lastname: Yih
authors.forename: Ting-Chao
authors.initials: TC
authors.lastname: Chou
authors.forename: Tsann-Long
authors.initials: TL
authors.lastname: Su
mesh_terms: D042462:4-Quinolones / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001557:Benzenesulfonates / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D042462:4-Quinolones; D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D014404:Tubulin; D050257:Tubulin Modulators