Synthesis, in vitro antimicrobial evaluation, and molecular docking studies of new isatin-1,2,3-triazole hybrids

Abstract Antibiotic resistance is rapidly evolving at an alarming rate, posing a severe threat to humanity. In an effort to develop compounds with antimicrobial activity, we synthesized a series of isatin-1,2,3-triazole hybrids 12-21 using the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions. Structural verification of the new isatin-1,2,3-triazole hybrids was accomplished using a variety of spectroscopic characterization techniques. The novel hybrids were evaluated for their in vitro antimicrobial activity against different pathogenic bacteria and fungi species using both agar well and disc-diffusion assays. Ampicillin and Nystatin were used as standard reference antimicrobial drugs. The antimicrobial evaluation revealed that the most active derivative is isatin-1,2,3-triazole 21. Moreover, the tested compounds are more active against Gram-negative bacteria than Gram-positive bacteria. Molecular docking revealed that compound 21 could bind to the active sites of D-alanine-D-alanine ligase and dihydrofolate reductase via multiple H-bonds, π-π, and CH-π interactions.