Benzotriazole-oxadiazole hybrid Compounds: Synthesis, anticancer Activity, molecular docking and ADME profiling studies
Citation
Arif Mermer a,⇑ , Muhammet Volkan Bulbul b,c , Semiha Mervenur Kalender b , Ilknur Keskin b , Burak Tuzun d , Ozan Emre Eyupoglu e aUniversity of Health Sciences Turkey, Experimental Medicine Research and Application Center, Uskudar, 34662, Istanbul, Turkey bDepartment of Histology and Embryology, School of Medicine, Istanbul Medipol University, Beykoz, 34810, Istanbul, Turkey cDepartment of Histology and Embryology, Faculty of Medicine, Nisantasi University, Sarıyer, 34398, Istanbul, Turkey d Plant and Animal Production Department, Technical Sciences Vocational School of Sivas, Sivas Cumhuriyet University, Sivas, Turkey eDepartment of Biochemistry, School of Pharmacy, Istanbul Medipol University, Beykoz, 34810, Istanbul, TurkeyAbstract
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, 13C 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.
