Hydrazinyldiene-chroman-2,4-diones in inducing growth arrest and apoptosis in breast cancer cells: Synergism with doxorubicin and correlation with physicochemical properties

• Published in: Acta Pharmaceutica 2017-03, Vol.67 (1), p.35-52
• Main Authors: Ballazhi, Lulzime, Imeri, Faik, Jashari, Ahmed, Popovski, Emil, Stojković, Goran, Dimovski, Aleksandar J., Mikhova, Bozhana, Mladenovska, Kristina
• Format: Article
• Language: English
• Subjects: breast cancer cells; cytotoxicity; doxorubicin; hydrazinyldiene chroman 2,4 diones; physicochemical properties
• ISSN: 1846-9558; 1330-0075; 1846-9558
• DOI: 10.1515/acph-2017-0006

This study evaluates the effects of previously synthesized hydrazinyldiene-chroman-2,4-diones on cell proliferation and apoptosis, cell cycle distribution and migration capacity of MCF-7 breast cancer cells in synergy with doxorubicin. Physicochemical properties of the synthesized compounds were correlated with their structure and activity. Significant cell viability decrease in comparison with the effect of doxorubicin alone and the reference 4-hydroxycoumarin was observed when combination treatment comprising doxorubicin and the title compounds was applied. Synergistic effect with doxorubicin was also observed in down-regulation of phospho-Thr Akt levels, confirming reduced proliferation and increased apoptosis. Combined treatment increased the percentage of cells arrested at the G /M stage. Additive inhibition of cell migration was also observed, pointing to the possibility of reducing the risk of metastases. With their solubility profile and log D , all the synthesized compounds follow Lipinski’s rule of five for good permeability (absorption) potential.