Synthesis, biological evaluation and network pharmacology based studies of 1,3,4-oxadiazole bearing azaphenols as anticancer agents

To discover novel and effective potential anticancer agents, a series of azophenol derivatives containing 1,3,4-oxadiazoles moiety was synthesized and investigated for their anticancer activities against several human can-cer cell lines by MTT method. Their structures were characterized by 1H NMR, 13C NMR, IR and HRMS spectral analyses. Among the prepared compounds, 5df displayed significant anti-proliferative activity against HCT116 cancer cells with an IC50 value of 4.09 +/- 0.04 mu M. Moreover, this compound had low cytotoxicity against normal cells. Flow cytometric analysis indicated that compound 5df arrested the cell cycle at S phase and induced apoptosis in a dose-dependent manner. Additionally, network pharmacology analysis calculated that 5df might target several key proteins, including AKT serine/threonine kinase 1 (AKT1), SRC proto-oncogene, non-receptor tyrosine kinase (SRC). Furthermore, molecular docking study indicated that 5df exhibited potentially high binding affinity to these target proteins with binding energies lower than-8 kcal/mol. These findings provide valuable insights for the development of azophenol derivatives as potential anticancer agents.