In order to develop new natural product-based anticancer agents, a series of 1,3,4-oxadiazole analogues based on petiolide A were prepared and evaluated for their anticancer activities by MTT method. The structures of all analogues were characterized by various spectral analyses, and B9 was further confirmed by X-ray crystallography. Among all the synthesized compounds, B1 displayed the most promising growth inhibitory effect on colon cancer cells (HCT116) with the IC 50 value of 8.53 μM. Flow cytometric analysis exhibited that B1 arrested the cell cycle at G2 phase and induced apoptosis. Additionally, network pharmacology analysis calculated that B1 might target several key proteins, including AKT serine/threonine kinase 1 (AKT1), SRC proto-oncogene, non-receptor tyrosine kinase (SRC) and epidermal growth factor receptor (EGFR). Furthermore, molecular docking study indicated that B1 had potentially high binding affinity to these three target proteins. Given these results, analogue B1 could be deeply developed as potential anticancer agents.
Keyphrases
- tyrosine kinase
- epidermal growth factor receptor
- molecular docking
- cell cycle
- induced apoptosis
- advanced non small cell lung cancer
- cell proliferation
- signaling pathway
- molecular dynamics simulations
- endoplasmic reticulum stress
- high resolution
- oxidative stress
- protein kinase
- computed tomography
- optical coherence tomography
- cell death
- mass spectrometry
- climate change
- structure activity relationship