Solution-Phase and Mechanochemical Synthesis and Antimicrobial Activity of New Thiazolo[3,2-<i>a</i>]Pyridine-6-Sulfonamides

This study focuses on the development of environmentally friendly and efficient synthetic routes for novel thiazolo[3,2-a]pyridine-6-sulfonamide derivatives with potential antimicrobial properties. Using a one-pot multi-component approach, these heterocyclic compounds were synthesized both in solution and under solvent-free mechanochemical conditions. Reactions between 1-(4-oxothiazolidin-2-ylidene)-N-phenylmethane sulfonamide, malononitrile, and aryl aldehydes led to two distinct classes of sulfonamides depending on the stoichiometry of the aldehydes used. A range of these compounds, along with structurally related analogues, was evaluated for antimicrobial activity against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Bacillus cereus. Five derivatives demonstrated significant activity, particularly against S. aureus, highlighting their potential as lead compounds in the development of new antibacterial agents.