Synthesis of New 1,2,4-Triazole Derivatives and Investigation of Their Matrix Metalloproteinase-9 (MMP-9) Inhibition Properties

Nine new 2-[[5-((4-acetamidophenoxy)methyl)-4-phenyl-4H-1,2,4-triazol-3-yl] thio]-N-(aryl/heteroaryl)acetamide (5a-5i) derivatives were synthesized and tested for their matrix metalloproteinase-9 (MMP-9) inhibition potency which is associated with antiproliferative activity.None of the compounds exhibited MMP-9 inhibition activity close to standard drug however, two compounds 5e bearing 6-methylbenzothiazole and 5g bearing 6-ethoxybenzothiazole moieties showed the highest MMP-9 inhibition which were determined over than 50% percentage at 100 μg/mL concentration.Some physicochemical properties of all final compounds were calculated via SwissADME and the results were modest to be able to an oral drug.Molecular docking studies were realized with MMP-9 enzyme (PDB ID: 5I12) and 5d, 5e, and 5g compounds for comparing the active and non-active/low effective structures.