Synthesis, antimicrobial activity, molecular docking and MD simulation studies, in silico ADME investigations and thermo-acoustic studies of heterocyclic dihydropyrimidine substituted 1,3,4-thiadiazole scaffolds

Abstract

The connections between the chemical structures and antibacterial properties of different functional groups including organic molecules were examined in this study. we have synthesized a novel series of 1,3,4-thiadiazole hybrids (5a-o) based on 3,4-dihydropyrimidines. After an effective synthesis, the compounds' structure was confirmed by using spectrum techniques like IR, 1H NMR, 13C NMR, and mass spectrometry. Elemental analyses were performed on a Perkin-Elmer 2400 CHN analyzer and the resulting data were within the accepted range (± 0.40) of the calculated values. The in vitro antimicrobial activity of the compounds against a range of bacterial and fungal species. Compound 5i showed potent inhibitory effects against P. aeruginosa with MIC values of 12.5 μg/ml S. aureus and A.niger were positively affected by compound 5k with MIC values of 12.5 μg/ml and 50 μg/ml, respectively. Based on the results, compounds 5a and 5o have moderate activity against C.albicans and E. coli with MIC values of 50 μg/ml and 62.5 μg/ml respectively. Furthermore, molecular docking and molecular dynamics simulations were used to identify the most stable conformation of newly discovered inhibitors. Thermo-acoustical properties of derivatives 5k and 5l in DMSO and DMF solvent have been determined at three different atmospheric pressure temperatures (298.15, 308.15, and 318.15)K. The components of the liquid mixture's molecular interactions have been taken into account to explain these results. The acquired results are interpreted in terms of interactions between solutes and solvents, providing insight into the compounds' potential to form or disrupt structures in DMSO and DMF solutions.