A new set of 5,6-dimethyl-2-(4-oxo-2-(substitutedphenyl)thiazolidin-3-ylamino)thieno2,3-id/ipyrimidin-4(3iH/i)-one compounds (5a-5j) was successfully synthesized using a rational multi-step synthetic strategy starting from ethyl-2-amino-4,5- dimethylthiophene-3-carboxylate. The synthetic route started with the formation of the thienopyrimidinone scaffold, followed by hydrazinolysis to give the corresponding hydrazine intermediate. The Schiff base reaction with various substituted aromatic aldehydes gave the key imine intermediates, which underwent cyclocondensation with thioglycolic acid to give the desired thiazolidinone hybrids. The protocol used proved efficient, as the desired compounds were obtained in good to excellent yields. All the newly synthesized compounds were fully characterized using elemental analysis and various spectroscopic techniques, including IR, sup1/supH NMR, sup13/supC NMR, and mass spectrometry, thus confirming the proposed molecular structures. The characteristic spectral data provided evidence for the successful incorporation of both the thienopyrimidine and thiazolidinone pharmacophores. The synthesized compounds were tested for their multi-target biological properties, including antibacterial, antifungal, and antioxidant activities. Antibacterial activity was tested against representative Gram-positive (iStaphylococcus aureus, Streptococcus pyogenes/i) and Gram-negative (iEscherichia coli, Pseudomonas aeruginosa/i) bacteria, while antifungal activity was tested against iCandida albicans, Aspergillus niger,/i and iAspergillus clavatus/i. In addition, antioxidant activity was determined using the 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay. Several compounds showed significant antimicrobial activity, especially those with electron-withdrawing substituents, indicating enhanced interaction with microbial targets. However, compounds with electron-donating substituents showed better antioxidant activity, indicating favorable radical scavenging capacity. The results suggest that thienopyrimidine–thiazolidinone hybrids constitute a promising class of multifunctional heterocycles, meriting further investigation for potential therapeutic applications.
Himanshu Patel (Fri,) studied this question.