Substituted E-3-(3-indolylmethylene)1,3-dihydroindol-2-ones with antiproliferative activity. Study of the effects on HL-60 leukemia cells

  • Eur J Med Chem. 2014 May 22:79:382-90. doi: 10.1016/j.ejmech.2014.04.004.
Alberto Leoni  1 ,  Alessandra Locatelli  1 ,  Rita Morigi  1 ,  Mirella Rambaldi  2 ,  Concettina Cappadone  1 ,  Giovanna Farruggia  1 ,  Stefano Iotti  1 ,  Lucia Merolle  1 ,  Maddalena Zini  3 ,  Claudio Stefanelli  4
Affiliations
  • 1. Department of Pharmacy and Biotechnology, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
  • 2. Department of Pharmacy and Biotechnology, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy. Electronic address: [email protected].
  • 3. Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy.
  • 4. Department for Life Quality Studies, University of Bologna, Rimini Campus, 47921 Rimini, Italy.
PMID: 24747749 DOI: 10.1016/j.ejmech.2014.04.004
Abstract

The synthesis of new substituted E-3-(3-indolylmethylene)1,3-dihydroindol-2-ones is reported. The antiproliferative activity was evaluated according to protocols available at the National Cancer Institute (NCI), Bethesda, MD. The action of the most active compound 10 was further investigated in HL-60 leukemia cells. Results obtained show that it causes a block in cell cycle progression, with cell arrest in the G2/M phase, associated with activation of Apoptosis accompanied with increased oxidative stress and deregulation of the homeostasis of divalent cations, with significant increase in the cellular concentrations of free CA(2+) and Mg(2+).

Keywords
Antiproliferative activity; Apoptosis; Divalent cations; Indolyl-indol-2-one; Knoevenagel reaction.