Antitubercular evaluation and synthesis of fused pyrano-thiazole-2-one derivatives via green and efficient protocol

Abstract

Tuberculosis has become one of the leading causes of mortality worldwide. In developing countries, tuberculosis is one of the 10th leading causes of death, highlighting the urgent need for antitubercular drugs. In this study, we synthesized fused pyrano-thiazole-2-one derivatives (4a-l) as potential antitubercular agents. To achieve this, we developed a straightforward and environmentally benign one-pot method. Substituted aromatic aldehydes (1a-l), malononitrile (2), and thiazolidine 2,4-dione (3) were subjected to a one-pot reaction with PEG-400 solvent and BEC catalyst in a microwave at 210 W for an hour to obtain 86–92% yield of the products. This synthetic approach not only aligns with the principles of green chemistry by reducing the use of hazardous solvents, but also improves the synthetic efficiency, product yield, and reaction time. IR, 1 H NMR, 13 C NMR and Mass spectroscopic techniques were used to confirm the structures. These confirmed derivatives were evaluated for their antitubercular activities at different concentrations ranging from 6.25 to 100 µg/mL against M. smegmatis (ATCC No. 19420) using the Microplate Alamar Blue Assay. Compound 4b was the most active with an MIC (6.19 µg/mL) against pathogens, followed by compounds 4c (11.01 6.19 µg/mL), 4g (12.19 6.19 µg/mL), and 4h (11.93 6.19 µg/mL). Additionally, molecular docking studies were performed to verify the interaction with the target protein (PDB ID: 2H7M). Several derivatives demonstrated significant activity to growth inhibition.