Design, synthesis, in vitro anti-oxidant evaluation, α-amylase inhibition assay, and molecular docking analysis of 2-(2-benzylidenehydrazinyl)-4,4-diphenyl-1H-imidazol-5(4H)-ones

• Published in: Journal of molecular structure Vol. 1278; p. 134924
• Main Authors: Aziz, Hamid, Saeed, Aamer, Jabeen, Farukh, Khan, Muhammad Aslam, Ur Rehman, Ashfaq, Khan, Muhammad Qasim, Saleem, Muhammad
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15.04.2023
• Subjects: Azomethine; Diabetes; Imidazole; Oxidation; Radicals; Reduction; Α-amylase; Reduction; Α-amylase; Imidazole; Azomethine; Oxidation; Diabetes; Radicals
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2023.134924

•Thiohydantoin-azomethine hybrids (4–6k) were synthesized and subjected to in vitro biological assays.•The screened compounds (4–6k) displayed excellent DPPH quenching potential.•The screened hybrids (4–6k) possess higher oxidative and lower reducing contents.•The hybrid compounds (4–6k) lack significant dose-dependent α-amylase inhibition.•Docking analysis suggests electron-withdrawing groups have better binding ability. Reactive oxygen and nitrogen species (RONS) regulate physiological processes to ensure cellular integrity. However, overproduction of RONS leads to oxidative stresses which results in certain disorders like Diabetes Mellitus. In this connection, the design, synthesis, in vitro anti-oxidant, antidiabetic, and molecular docking (MD) analysis of a series of thiohydantoin-azomethine hybrids was carried out. Their oxidative potential was revealed from in vitro% DPPH quenching, phosphomolybdenum, and ferric (Fe3+) ion-reducing assays. Consequently, most of the screened compounds displayed excellent dose-dependent in vitro response as evident by their higher% DPPH free radical scavenging potential. The screened 2-hydrazinyl-4,4-diphenyl-1H-imidazol-5(4H)-one displayed the highest DPPH scavenging potential with IC50 values of 98.23 µg/mL and the associated DPPH free radical scavenging of 87.14%. Similarly, the screened compounds were found to have higher total anti-oxidant contents than their reducing contents. Moreover, the synthesized compounds were subjected to in vitro screening against the α-amylase enzyme. Most of the screened compounds lack pronounced dose-dependent responses, associated with lower% α-amylase inhibitory potential, and higher IC50 values. The most potent compound 2-(2-(4-(dimethylamino)benzylidene)hydrazinyl)-4,4-diphenyl-1H-imidazol-5(4H)-one displayed notable inhibition (65%) with IC50 value of 120.3 µg/mL using Acarbose as a reference standard. Furthermore, molecular docking analysis revealed that the screened compounds bind well within the active site of the α-amylase enzyme. The compounds bearing electron-withdrawing groups displayed better binding potential in comparison to those having electron-donating substituents. [Display omitted]