2. Academic Validation
  3. Substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones and analogues: synthesis, cytotoxic activity, and study of the mechanism of action

Substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones and analogues: synthesis, cytotoxic activity, and study of the mechanism of action

  • J Med Chem. 2012 Mar 8;55(5):2078-88. doi: 10.1021/jm2012694.
Aldo Andreani 1,  Massimiliano Granaiola,  Alessandra Locatelli,  Rita Morigi,  Mirella Rambaldi,  Lucilla Varoli,  Natalia Calonghi,  Concettina Cappadone,  Giovanna Farruggia,  Claudio Stefanelli,  Lanfranco Masotti,  Tam L Nguyen,  Ernest Hamel,  Robert H Shoemaker
Affiliations

Affiliation

  • 1 Dipartimento di Scienze Farmaceutiche, Università di Bologna, Via Belmeloro 6, 40126 Bologna, Italy. aldo.andreani@unibo.it
PMID: 22283430 DOI: 10.1021/jm2012694
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.

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