title: Substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones and analogues: synthesis, cytotoxic activity, and study of the mechanism of action.
abstract: The synthesis of substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones and analogues is reported. Their cytotoxic activity was evaluated according to protocols available at the National Cancer Institute (NCI), Bethesda, MD. The action of selected compounds was examined for potential inhibition of tubulin assembly in comparison with the potent colchicine site agent combretastatin A-4. The most potent compounds also strongly and selectively inhibited the phosphorylation of the oncoprotein kinase Akt in cancer cells. The effect of the most interesting compounds was examined on the growth of HT-29 colon cancer cells. These compounds caused the cells to arrest in the G2/M phase of the cell cycle, as would be expected for inhibitors of tubulin assembly.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Bologna, Via Belmeloro 6, 40126 Bologna, Italy. aldo.andreani@unibo.it
authors.forename: Aldo
authors.initials: A
authors.lastname: Andreani
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Granaiola
authors.forename: Alessandra
authors.initials: A
authors.lastname: Locatelli
authors.forename: Rita
authors.initials: R
authors.lastname: Morigi
authors.forename: Mirella
authors.initials: M
authors.lastname: Rambaldi
authors.forename: Lucilla
authors.initials: L
authors.lastname: Varoli
authors.forename: Natalia
authors.initials: N
authors.lastname: Calonghi
authors.forename: Concettina
authors.initials: C
authors.lastname: Cappadone
authors.forename: Giovanna
authors.initials: G
authors.lastname: Farruggia
authors.forename: Claudio
authors.initials: C
authors.lastname: Stefanelli
authors.forename: Lanfranco
authors.initials: L
authors.lastname: Masotti
authors.forename: Tam L
authors.initials: TL
authors.lastname: Nguyen
authors.forename: Ernest
authors.initials: E
authors.lastname: Hamel
authors.forename: Robert H
authors.initials: RH
authors.lastname: Shoemaker
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003078:Colchicine / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008958:Models, Molecular; D010766:Phosphorylation; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014404:Tubulin / Q000737:chemistry; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D007211:Indoles; D013844:Thiazoles; D014404:Tubulin; D050257:Tubulin Modulators; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D003078:Colchicine