title: Synthesis and biological evaluation of combretastatin-amidobenzothiazole conjugates as potential anticancer agents.
abstract: A series of combretastatin-amidobenzothiazole conjugates have been synthesized and evaluated for their anticancer activity. All these compounds exhibited significant anticancer activity and the most potent compound (11a) showed GI(50) values ranging 0.019-11 μM. Biological studies such as cell cycle distribution, effect on tubulin polymerization and effect on ERK signalling pathway have been examined in MCF-7 cell line. FACS analysis revealed that these compounds induced cell cycle arrest at G2/M phase. Compound 11a showed significant effect on tubulin polymerization and affected the ERK signalling pathway that result in the decreased levels of ERK1/2, p-ERK and c-Jun proteins. Docking experiments have shown that the active molecules interact and bind well in the ATP binding pocket of ERK protein.
authors.affiliation: Division of Organic Chemistry, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 607, India. ahmedkamal@iict.res.in
authors.forename: Ahmed
authors.initials: A
authors.lastname: Kamal
authors.forename: Adla
authors.initials: A
authors.lastname: Mallareddy
authors.forename: M
authors.initials: M
authors.lastname: Janaki Ramaiah
authors.forename: S N C V L
authors.initials: SN
authors.lastname: Pushpavalli
authors.forename: Paidakula
authors.initials: P
authors.lastname: Suresh
authors.forename: Chandan
authors.initials: C
authors.lastname: Kishor
authors.forename: J N S R C
authors.initials: JN
authors.lastname: Murty
authors.forename: N Sankara
authors.initials: NS
authors.lastname: Rao
authors.forename: Sowjanya
authors.initials: S
authors.lastname: Ghosh
authors.forename: Anthony
authors.initials: A
authors.lastname: Addlagatta
authors.forename: Manika
authors.initials: M
authors.lastname: Pal-Bhadra
mesh_terms: D050256:Antimitotic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D052160:Benzothiazoles / Q000737:chemistry / Q000494:pharmacology*; D001632:Bibenzyls / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D061986:MCF-7 Cells; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D058105:Polymerization; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D050256:Antimitotic Agents; D052160:Benzothiazoles; D001632:Bibenzyls; D014404:Tubulin; C040105:combretastatin