Novel Hydrazide-Hydrazone Derivatives Containing Flurbiprofen 1,2,4-Triazole as Anticancer Agents: Design, Synthesis and Biological Evaluation

Abstract

Hydrazone derivatives are one of the scaffolds frequently used in new drug development studies. Due to the promising pharmacological effects of the hydrazone structure, fifteen new hydrazide-hydrazone compounds containing flurbiprofen 1,2,4-triazole were synthesized in this study and their in vitro anticancer effects were tested. All compounds were tested for cytotoxic effects against breast cancer cell lines (MCF-7 and MDA-MB231), and glioblastoma cell line (U87) by using MTT assay. Among the synthesized compounds, compounds 7a and 7c exhibited the most potent cytotoxic activity with IC50 values of 7.80 +/- 1.20 & micro;M and 2.40 +/- 0.93 & micro;M against MCF-7 cell line, while compound 7a showed the highest activity with IC50 value of 7.63 +/- 1.05 & micro;M against MDA-MB231 cell line. In addition, compounds 7c and 7n presented cytotoxic activity with IC50 values of 10.31 +/- 4.63 & micro;M and 10.81 +/- 6.11 & micro;M against U87 cell line. The possible cytotoxic effects of compounds on mouse fibroblast cell line (L929) were assessed for their safety and compounds 7a, 7c, and 7n were found less toxic than 5-fluorourasil. Additionally, compound 7c was further studied to investigate its effects on apoptosis and PI3K activity, which play a role in cancer development. The results showed that compound 7c increased apoptosis in MCF-7 cells and it displayed PI3K enzyme inhibitory activity. Our study revealed that the synthesized hydrazone compounds have the potential to be lead compounds for further studies on cancer.