Design, Synthesis, Molecular Docking, and Antimicrobial Evaluation of Novel 1,3-thiazolidine-4-one Derivatives Incorporating Pyridine Scaffold

Background: In this study, novel 1-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2H)-yl)-3-phenylthiourea 2, 3-phenylthiazolidin-4-one 3, and arylidene-4-thiazolidinone deriva-tives 5a-k were synthesized in excellent yields. The produced compounds underwent assess-ment for their antimicrobial properties. Efficient and easy procedures for synthesizing aryli-dene-4-thiazolidinones 5a-k were delineated. Materials and Methods: 3-phenylthiazolidin-4-one 3 was achieved by reacting 1-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2H)-yl)-3-phenylthiourea 2 with ethyl 2-bromoacetate in EtOH, employing anhydrous sodium acetate at reflux temperature. Furthermore, a sequence of aryli-dene-4-thiazolidinone derivatives 5a-k was synthesized by condensing 4-thiazolidinone 3 with different aromatic and heterocyclic aldehydes in a refluxing EtOH-containing piperidine. The binding mechanism of the thiazolidine derivatives to the dihydrofolate reductase (DHFR) and rhomboid protease proteins was determined by docking studies. Results: Compounds 2, 5c, 5d, 5g, and 5i exhibited germicidal effects against both Gram-negative and Gram-positive bacteria. Furthermore, these compounds exhibited antifungal properties. The MIC ranged from 250 to below 500 μg/mL. The docking study revealed a strong correlation between the docking solutions and the experimental observations. Conclusion: The structure of new compounds was identified by analytical and spectroscopic data. Certain thiazolidines showed exceptional antibacterial and antifungal properties. These interactions require more investigations that are comprehensive