β-Ionone derived apoptosis inducing endoperoxides; Discovery of potent leads for anticancer agents

A series of endoperoxides (3a-j) were synthesized and evaluated for cytotoxic activity against four human cancer cell lines by using SRB dye assay. All the compounds displayed moderate to high cytotoxic effect against almost all investigational cancer cells. Particularly, compounds bearing electron withdrawing groups such as nitro substituted compound 3j (IC50 = 0.001 mu M) and fluor substituted compound 3i (IC50 = 0.003 mu M) showed comparatively more cytotoxic potential than standard drugs against lung cancer cell line (A549). All synthesized endoperoxides (3a-j) were further evaluated for their apoptotic potential through various parameters such as flow-cytometric analysis of nuclear DNA, flow-cytometric determination of mitochondrial membrane potential (Delta Psi(m)), spectrofluorimetric estimation of intracellular ROS level and caspase-3 & 9 assays in treated lung cancer cells (A549); results reveal that endoperoxides induce apoptosis in cancer cells via mitochondrial pathway. (C) 2014 Elsevier Masson SAS. All rights reserved.