Novel Ag(I)‐based 1,2,4‐Oxadiazole Complexes: Synthesis, X‐Ray Crystal Structure, and Biological Evaluation as Anticancer Candidates

ABSTRACT The 3,5‐diaryl‐1,2,4‐oxadiazole scaffolds 2 and 3 were synthesized and used as ligands to obtain three novel Ag(I) complexes 4–6 . The structure of the Ag(I) complexes 4–6 has been confirmed by single crystal X‐ray diffraction. Complex 4 has the dinuclear formula [Ag(2)(NO 3 )] 2 . 5 and 6 are monomeric complexes having the formula [Ag(3) 2 (NO 3 )] and [Ag(3) 2 ]ClO 4 , respectively. In vitro, trypsin, ALDH2, and iNOS inhibition activities were assessed for the free ligands and their Ag(I) complexes. Interestingly, Ag(I) complexes 4–6 revealed more prominent trypsin inhibitory activity than the ligands 2 and 3 . The oxadiazole derivative 3 and its Ag(I) complex ( 6 ) showed significant ALDH2 inhibition (45% and 55%, respectively). Complex 6 (IC 50 = 35.61 μM) surpassed its 1,2,4‐oxadiazole ligand 3 (IC 50 = 88 μM) and evidenced the most prominent ALDH2 inhibitory activity. The oxadiazole derivative 3 and its corresponding Ag(I) complexes 5 and 6 showed significant iNOS inhibition (77.77%, 84.12%, and 84.15%, respectively). With IC 50 values of 18.13, 18.15, and 13.96 μM, respectively, complex 6 is the most potent against iNOS, surpassing the reference standard.