Suzuki‐Miyaura Synthesis, UV, TD‐DFT, and COX Docking Comparative Studies of Fluorinated Biphenyl‐1,2,4‐oxadiazole
Mohammed Salah Ayoup, Amal Yousri, Saied M. Soliman, Mohamed S. Nafie, Amr Negm, Yasair S. Al‐Faiyz, Amr Sonousi, Faisal Mohammed Alkahtani, Ibrahim ElghamryABSTRACT
Synthesis of the novel 4‐trifluoromethylbiphenyl‐based 1,2,4‐oxadiazole 8 was accomplished via Suzuki‐Miyaura cross‐coupling. A comparative study of the UV–vis spectra between the theoretical and experimental results for 8 with p ‐CF 3 or o ‐CF 3 phenyl‐1,2,4‐oxadiazole derivatives 4 and 5, respectively, were conducted. The observed UV‐vis spectra confirmed the presence of π→π*, n→π*, and electronic transitions. The respective maximum absorption wavelengths (λ max ) for 4 , 5, and 8 are 245–270, 315–320, and 220 nm. Furthermore, TD‐DFT theory confirmed the potential of using the three derivatives as UV absorbers with high energy gap values (4.51‐5.00 eV) for major contributions in the reported compounds. Compounds 4, 5 , and 8 have COX‐2 IC 50 values of 0.29, 0.93, and 1.05 µM, respectively. 4 has the highest SI = IC 50 COX‐1/IC 50 COX‐2) (56.2) among the new analogs exceeds the reference standard Celecoxib (37.6), indicating it is the highest inhibition activity for COX‐2 than compounds 5 or 8 . As a promising anti‐inflammatory agent. The molecular docking of 4 showed stable interactions and a low‐energy docking pose (−6.31 Kcal/mol) and strong biological affinity for COX‐2. In contrast, docking of 4 into the COX‐1 active site revealed no stable binding orientation.