Facile synthesis of fused imidazo[1,2-a]pyridine-benzo[4,5]isothiazolo[2,3-c] [1,2,3]triazoles as potent antibacterial agents
摘要
In this report, we developed a series of novel fused imidazo[1,2-a]pyridine-benzo [4,5]isothiazolo[2,3-c] [1,2,3]triazoles derivatives in a one-pot method under microwave conditions by using iodoalkyne, sulfonamide, and triflyl azide. This method enables the synthesis of fused 1,2,3-triazoles via Cu(I)-catalysed cycloaddition and C-C bond coupling in shorter reaction times and with good to excellent yields. Later, antimicrobial activity was evaluated for the synthesized compounds (6a-6n) against three Gram-positive bacterial strains, B. subtilis, S. aureus, and S. epidermidis. Among all compounds, 6k has shown ≈ 2-fold more potent against the three tested bacterial strains with MIC values 1.56 ± 0.23 to 3.12 ± 0.43 µg/mL. Similarly, compound 6 L has shown ≈ 2-fold more potent against S. aureus and S. epidermidis with IC50 values 3.12 ± 0.47 and 3.12 ± 0.38 µg/mL, and equipotent against B. subtilis with IC50 value 3.12 ± 0.54 µg/mL. Compounds 6 g and 6n have shown equipotent activity against B. subtilis and S. aureus, comparable to standard dicloxacillin. Later, more potent compounds were screened for their in silico molecular docking studies against Penicillin-binding protein, and compounds 6f, 6k, and 6 L have shown similar H-bonding interactions with dicloxacillin, and these three compounds have shown the highest binding energies with − 8.04 to -8.97 Kcal/mol.
Graphical abstractSAR of target fused 1,2,3-triazoles (6a-6n)