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

Abstract

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 cancer 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 µM. 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.