title: 3-substituted 2-phenylimidazo[2,1-b]benzothiazoles: synthesis, anticancer activity, and inhibition of tubulin polymerization.
abstract: A new series of 3-substituted 2-phenylimidazo[2,1-b]benzothiazoles (3 a-h) were synthesized by C-arylation of 2-arylimidazo[2,1-b]benzothiazoles using palladium acetate as catalyst, and the resulting compounds were evaluated for their anticancer activity. Compounds 3 a, 3 e, and 3 h exhibited good antiproliferative activity, with GI50 values in the range of 0.19-83.1 μM. Compound 3 h showed potent anticancer efficacy against 60 human cancer cell lines, with a mean GI50 value of 0.88 μM. This compound also induced cell-cycle arrest in the G2/M phase and inhibited tubulin polymerization followed by activation of caspase-3 and apoptosis. A high-throughput tubulin polymerization assay showed that the level of inhibition for compound 3 h is similar to that of combretastatin A-4. Molecular modeling studies provided a molecular basis for the favorable binding of compounds 3 a, 3 e, and 3 h to the colchicine binding pocket of tubulin.
authors.affiliation: Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500607, India. ahmedkamal@iict.res.in
authors.forename: Ahmed
authors.initials: A
authors.lastname: Kamal
authors.forename: Farheen
authors.initials: F
authors.lastname: Sultana
authors.forename: M Janaki
authors.initials: MJ
authors.lastname: Ramaiah
authors.forename: Y V V
authors.initials: YV
authors.lastname: Srikanth
authors.forename: A
authors.initials: A
authors.lastname: Viswanath
authors.forename: Chandan
authors.initials: C
authors.lastname: Kishor
authors.forename: Pranjal
authors.initials: P
authors.lastname: Sharma
authors.forename: S N C V L
authors.initials: SN
authors.lastname: Pushpavalli
authors.forename: Anthony
authors.initials: A
authors.lastname: Addlagatta
authors.forename: Manika
authors.initials: M
authors.lastname: Pal-Bhadra
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use; D052160:Benzothiazoles / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D001665:Binding Sites; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003078:Colchicine / Q000737:chemistry; D003198:Computer Simulation; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy; D058105:Polymerization / Q000187:drug effects; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry* / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D052160:Benzothiazoles; D007093:Imidazoles; D014404:Tubulin; D050257:Tubulin Modulators; C029899:imidazole; D003078:Colchicine