Synthesis, Characterization, DFT Computation, and Antimicrobial Activity of Novel Biginelli Compounds

(2E)-3-(Dimethylamino)-1-(2,4,5-trimethoxyphenyl)prop-2-en-1-one was obtained by the reaction of 2,4,5-trimethoxyacetophenone with N,N-dimethylformamide dimethyl acetal (DMF-DMA) by refluxing without a solvent for 12 h. The resulting enaminone was reacted with substituted benzaldehydes, thiourea in glacial acetic acid which acted as a catalyst to afford novel dihydropyridine-2(1H)-thione derivatives 3a–3j in good yield. Spectroscopic methods like FT-IR, ¹H NMR, ¹³C NMR, and GC/MS and elemental analysis were employed to confirm and characterize the structures of all newly synthesized compounds. The density functional theory (DFT) analysis with a hybrid correlation functional (B3LYP) and 6-311++G(d,p) basis set was used to optimize the geometry of the synthesized compounds. The charge transfer in their molecules was analyzed by calculations of the HOMO and LUMO energies. The molecular docking study demonstrated that dihydropyridine-2(1H)-thione derivatives 3a–3j bind well to the multidrug transporter ABCG2 via interactions comparable to the native co-crystallized inhibitor MZ29. All compounds of the series were tested for antimicrobial activity and were found to be active against different Gram-positive and Gram-negative bacterial, as well as fungal strains. Compound 3j containing a 3,4-dimethoxyphenyl substituent showed the most promising activity against all the tested strains.