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.
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.
Andreani
Aldo
A
Dipartimento di Scienze Farmaceutiche, Universita di Bologna, Via Belmeloro 6, 40126 Bologna, Italy. aldo.andreani@unibo.it
Burnelli
Silvia
S
Granaiola
Massimiliano
M
Leoni
Alberto
A
Locatelli
Alessandra
A
Morigi
Rita
R
Rambaldi
Mirella
M
Varoli
Lucilla
L
Calonghi
Natalia
N
Cappadone
Concettina
C
Voltattorni
Manuela
M
Zini
Maddalena
M
Stefanelli
Claudio
C
Masotti
Lanfranco
L
Shoemaker
Robert H
RH
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
D000970:Antineoplastic Agents; D007211:Indoles; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D013830:Thiadiazoles; D013844:Thiazoles