New 1,2,4-triazole-Chalcone hybrids induce Caspase-3 dependent apoptosis in A549 human lung adenocarcinoma cells

作者：Ahmed Fatma F; Abd El Hafeez Amer Ali^*; Abbas Samar H^*; Abdelhamid Dalia; Abdel Aziz Mohamed

来源：European Journal of Medicinal Chemistry, 2018, 151: 705-722.

DOI：10.1016/j.ejmech.2018.03.073

• 1, 2, 4-Triazole
• Chalcone
• Caspase-3
• Apoptosis
• A549 human lung
• NCI

A series of novel 1, 2, 4-triazole/ichalcone hybrids was prepared and identified with different spectroscopic techniques. The prepared compounds showed remarkable cytotoxic activity against different cancer cell lines. Compounds 24, 25, 27, 41 and 47 had shown the highest cytotoxicity among the tested compounds against human lung adenocarcinoma A549 cells with IC50 ranging from 4.4 to 16.04 mu M compared to cisplatin with IC50 of 153 mu M. Flow cytometric analysis of the tested compounds showed an increase in the number of apoptotic cells in a dose-dependent manner. The further mechanistic study demonstrated that 1, 2, 4-triazole-chalcone hybrids induced apoptosis via increased level of proapoptotic protein Bax, release of cytochrome c from mitochondria and activation of caspase-3/8/9 proteins. However, general caspase inhibition by the pan-caspase inhibitor, z-VAD-fmk, significantly decreased the apoptosis induced by the tested hybrids, suggesting dependency of apoptosis on activation of the caspase-3 pathway.

• 出版日期2018-5-10