Syeda Abida Ejaz, Mariia Miliutina, Peter Langer, Aamer Saeed* and Jamshed Iqbal* Pages 883 - 891 ( 9 )
Background: Previously, we have identified 3,3′–carbonyl–bis(chromones) (1a-h, 5e) and 3–(5–(benzylideneamino)thiozol–3–yl)–2H–chromen–2–ones (7a-j) as potent inhibitors of tissue non-specific alkaline phosphatase (TNAP). The present study was designed to investigate the cytotoxic and pro-apoptotic effect of the said derivatives.Methods: The anti-proliferative effect of the derivatives was investigated in three cancer cell lines i.e., MCF-7, K-562, HeLa and normal BHK21 cells using MTT assay. The pro-apoptotic effect of the most potent derivatives was investigated by using flow cytometry, DAPI and PI staining and DNA binding studies. Results: Among all the screened compounds, 1f, 1d, 1c (from 3,3′–carbonyl–bis(chromones), 7c, 7h and 7i (from 3–(5–(benzylideneamino)thiozol–3–yl)–2H–chromen–2–ones) exhibited remarkable growth inhibitory effects. Compounds 1f and 7c were found to be the most potent cytotoxic derivatives against MCF-7; 1d and 7h inhibited most of the proliferation of K-562 cells, whereas 1c and 7i showed maximum growth inhibition in HeLa cells. The identified compounds exerted lower micromolar potency against the respective cell line with significant selectivity over the normal cells (BHK–21). The identified compounds also induced either G2 or S-phase arrest within the respective cancer cells, chromatin condensation and nuclear fragmentation, as well as maximum interaction with DNA. Conclusions: These results provide evidence that the characteristic chemical features of attached groups are the key factors for their anticancer effects and play a useful role in revealing the mechanisms of action in relation to the known compounds in future research programs.
Alkaline phosphatase, breast cancer cells (MCF–7), bone marrow cells, cervical cancer cells (HeLa), anti-cancer effect, cell-cycle arrest.
Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad-22060, Institut für Chemie, Universität Rostock, Albert Einstein Str. 3a, 18059 Rostock, Institut für Chemie, Universität Rostock, Albert Einstein Str. 3a, 18059 Rostock, Department of Chemistry, Quaid-i-Azam University, Islamabad-45320, Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad-22060