Novel thiazolo[5,4-b]pyridine–sulfonamide conjugates: Synthesis, structure–activity relationship, and molecular docking studies

A series of thiazolo[5,4-b]pyridine–based sulfonamide derivatives was designed and synthesized using a cyanoacetyl sulfonamide intermediate to access various heterocyclic frameworks. Their antimicrobial activity was evaluated in vitro against Staphylococcus aureus , Escherichia coli , and Candida albicans using agar diffusion and minimum inhibitory concentration (MIC) determination. Several compounds exhibited potent antibacterial activity with MIC values ranging from 3.125 to 12.5 μg/mL, where compounds 10 , 16 , and 21 showed broad-spectrum activity comparable to or superior to reference drugs. Structure–activity relationship (SAR) analysis indicated that electron-withdrawing and aromatic substituents enhanced antimicrobial potency. Molecular docking studies against dihydrofolate reductase (DHFR, PDB ID: 2W9S) supported the experimental results, revealing favorable binding interactions and high affinity of the most active compounds. These findings suggest that thiazolo[5,4-b]pyridine–sulfonamide hybrids represent promising scaffolds for the development of new antimicrobial agents.