title: Antitumor activity of new substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones and 3-(5-imidazo[2,1-b]thiadiazolylmethylene)-2-indolinones: selectivity against colon tumor cells and effect on cell cycle-related events.
abstract: The synthesis of new 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones and 3-(5-imidazo[2,1-b]thiadiazolylmethylene)-2-indolinones is reported. The antitumor activity was evaluated according to the protocols available at the National Cancer Institute (NCI), Bethesda, MD. To investigate the mechanism of action of the most potent antitumor agent of this series, its effect on growth of HT-29 colon carcinoma cells was studied. Its ability to inhibit cellular proliferation was mediated by cell cycle arrest at the G2/M phase, accompanied by inhibition of ornithine decarboxylase (ODC), the limiting enzyme of polyamine synthesis, and followed by induction of apoptosis.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Universita di Bologna, Via Belmeloro 6, 40126 Bologna, Italy. aldo.andreani@unibo.it
authors.forename: Aldo
authors.initials: A
authors.lastname: Andreani
authors.forename: Silvia
authors.initials: S
authors.lastname: Burnelli
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Granaiola
authors.forename: Alberto
authors.initials: A
authors.lastname: Leoni
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: Manuela
authors.initials: M
authors.lastname: Voltattorni
authors.forename: Maddalena
authors.initials: M
authors.lastname: Zini
authors.forename: Claudio
authors.initials: C
authors.lastname: Stefanelli
authors.forename: Lanfranco
authors.initials: L
authors.lastname: Masotti
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; D001665:Binding Sites / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D016195:G2 Phase / Q000187:drug effects*; D019073:HT29 Cells; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D013830:Thiadiazoles; D013844:Thiazoles