Multicomponent Biginelli’s Synthesis, Antimycobacterial Activity and Molecular Docking Studies of Dihydropyrimidine Derivatives as Thymidylate Kinase Protein Targets

Background and Objective: Various biginelli compounds (dihydropyrimidinones) have been synthesized efficiently and in high yields under mild, solvent free and eco-friendly conditions in a one pot reaction of 1, 3-dicarbonyl compounds, aldehydes and urea/thiourea using Sodium Dodecyl Sulphate (SDS) as a novel catalyst under two experimental conditions. Methodology: The obtained products have been identified by spectral data (1H-NMR, IR and Mass) and their melting points. The dihydropyrimidinone derivatives were evaluated for their in vitro antimycobacterial activity against H37Rv strain by using alamar blue dye method. Results: The synthesized compounds exhibited promising activity (MIC: 6.25-100 μg mLG1) against mycobacterium tuberculosis H37Rv strain. Docking studies were carried out on synthesized dihydropyrimidines (DHPMs) using GOLD software, with the crystal structure of thymidylate kinase (1G3U) to gain some structural insights on the binding mode and possible interactions with the active site. Conclusion: Among the tested compounds, IVf was found to be most potent with Minimum Inhibitory Concentration (MIC): 6.2±0.36 μg mLG1 with least minimal toxicity some of them were found to possess significant activity, when compared to standard drug. The docking results revealed useful information to understand the interaction mode between dihydropyrimidine derivatives and thymidylate kinase (TMPK) and will facilitate the next cycle of drug design to explore the newer lead molecules.