Synthesis, molecular modeling and antioxidant activity of new thiadiazolyl-triazole analogues

Abstract

The synthetic protocol of our targeted thiadiazolyl-triazole hybrids is initiated by production of the precursor thiadiazolyl-triazole compound 4 by heterocyclizing 2-((1,3,4-thiadiazol-2-yl)amino)-2-oxo-N-phenylacetohydrazonoyl cyanide (3) with hydrazine hydrate. The precursor 4 was utilized for the preparation of the thiazolidinylidene thiadiazolyl-triazole analogues 6 and 7 through chloroacetylation followed by cyclization with ammonium thiocyanate. The DFT quantum chemical calculations were utilized in the determination of the frontier molecular orbitals energies and Fukui’s indices. The data showed that they have a low HOMO-LUMO energy gap ranging from 1.95 to 3.13 eV, for 7c and 5, respectively. The newly synthesized thiadiazole-triazole analogues were screened for antioxidant activity using the DPPH technique. In comparison to Vitamin C and BHT (Butylated hydroxytoluene) as controls, the analogues 5 and 7a-c demonstrated the highest inhibitions through IC50 values ranging from 22.63 to 31.71 µg/mL. Moreover, the molecular docking study of the produced thiadiazolyl-triazole analogues employ protein (PDB ID: 1HD2). The docking results were agreeable and established with the findings of the antioxidant examination.

Keywords

• Thiadiazole-triazole
• Thiazolidinone
• DFT/B3LYP
• Antioxidant
• Molecular docking