Microwave expedited Cu(I) catalyzed regioselective 1,2,3-triazoles as Mycobacterium Tuberculosis H37Rv inhibitors, in vitro Alpha-amylase and Alpha-glucosidase inhibition, in silico studies

Abstract

In the present study, an efficient and convenient synthesis of novel 1,2,3-triazoles (8i-t) incorporated quinoline and coumarin cores has been reported. Microwave-assisted Huisgen 1,3-dipolar cycloaddition reaction of azide and alkyne resulted in high yields (88-94 percent) of the title compounds. Regioselective single-product formation both under conventional and microwave methods is the foremost supremacy of this work. All the molecules were subjected to in vitro antibacterial assessment wherein the compounds 8i, 8k, 8l, 8n, and 8r demonstrated very good antibacterial activity against other bacterial strains tested. Compounds 8i, 8k, 8l, 8n, 8o, 8q, and 8r demonstrated excellent antitubercular activity with MICs in the range 1.60-6.25 Mu g/mL in comparison to the standard drugs (Isoniazid-1.60 Mu g/mL, Ciprofloxacin-3.25 Mu g/mL, Pyrazinamide-6.25 Mu g/mL). Compounds 8i, 8n, and 8r also exhibited inhibitory effects against Alpha-amylase and Alpha-glucosidase and thus, also showed anti-diabetic activity. The significantly active compounds were subjected to molecular docking and molecular dynamics simulation studies to study the putative binding pattern as well as the stability of the docked complexes, respectively. In silico ADME profiles of the titled compounds were also predicted to access the drug-likeness properties of the designed compounds. Titled compounds showed potential effectiveness as antibacterial and antidiabetic agents.