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

• DOI: 10.1016/j.ejmech.2014.04.004
• Publication Date: 2014-04-03T11:19:05Z
• Authors: Alberto Leoni; Alessandra Locatelli; Rita Morigi; Mirella Rambaldi; Concettina Cappadone; Giovanna Farruggia; Stefano Iotti; Lucia Merolle; Maddalena Zini; Claudio Stefanelli
• Keywords: 0301 basic medicine; Indoles; Cell Death; Dose-Response Relationship, Drug; Molecular Structure; Cell Cycle; Antineoplastic Agents; HL-60 Cells; Indolyl-indol-2-one; Knoevenagel reaction; Antiproliferative activity; Apoptosis; 3. Good health; Oxidative Stress; Structure-Activity Relationship; 03 medical and health sciences; Tumor Cells, Cultured; Humans; Drug Screening Assays, Antitumor; Cell Proliferation

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+).