Herein the designed novel benzotriazole-oxadiazole hybrid compounds were synthesized using both conventional method and ultrasound sonication (US) as an environmentally friendly method. It was observed that the US method provided an increase in reaction yields by reducing the reaction time approximately 3-fold. The synthesized compounds were investigated against PANC-1 cell line. All obtained compounds were characterized by FT-IR, 1H NMR, C-13 NMR and MS spectroscopic techniques. The compounds 4b and 4d exhibited very promising anticancer activity results with IC50 values of 117.5 +/- 0.084 lM and 87.82 +/- 4.319 lM, respectively. Further, molecular docking studies to suggest how the synthesized compounds interact with the kinase domain of human DDR1 in complex of pancreatic Cancer proteins (PDB ID: 6HP9), and the crystal structure of PDEd of pancreatic Cancer proteins (PDB ID: 5E80). It was concluded from the docking studies that the compound 4d demonstrated the highest binding score values for active site of both proteins. Afterwards, ADME calculations were performed to examine the drug properties of benzotriazole-oxadiazole hybrid compounds. (C) 2022 Elsevier B.V. All rights reserved.