SYNTHESIS, AND COMPUTATIONAL INVESTIGATION OF A 3,4- DIHYDROPYRIMIDINE-2(1H)-ONE DERIVATIVE: DFT, ADME, AND MOLECULAR DOCKING STUDIES

A 3,4-dihydropyrimidine-2(1H)-one derivative was synthesized via aone-pot condensation reaction involving 4-nitrobenzaldehyde, urea,and ethyl acetoacetate, with sulfamic acid serving as a mild and ecofriendlycatalyst in ethanol. The structure was confirmed by FT-IR, 1Hand 13C NMR spectroscopy. Density Functional Theory (DFT)calculations at the B3LYP/6-311++G(d,p) level provided optimizedgeometries, bond lengths, bond angles, revealing a partially planar,conjugated framework stabilized by resonance across the pyrimidine,ester, and nitrophenyl moieties. Frontier molecular orbital analysisshowed a HOMO–LUMO gap of 4.09 eV, suggesting moderatechemical reactivity. Molecular electrostatic potential (MEP) mappingidentified regions of high electron density around electronegativeatoms and electron-deficient zones over hydrogen atoms, providinginsight into possible reactive sites and non-covalent interactions. Insilico ADME evaluation predicted favorable pharmacokinetic anddrug-likeness properties, including good solubility, highgastrointestinal absorption, and compliance with Lipinski’s rule offive. Molecular docking revealed stable interactions with sterol 14-αdemethylase (CYP51) and E. coli DNA gyrase B. Key interactions with CYP51 included aconventional hydrogen bond with TYR132, a carbon–hydrogen bond with ILE304, a π–donorhydrogen bond with TYR118, hydrophobic and π–alkyl interactions with PHE228 andHIS310, and a π–alkyl interaction with the heme group (HEM601). Docking with DNA gyrase B showed π–cation interactions with ARG76, π–anion interactions with GLU50, andhydrophobic contacts with ILE78 and ILE94. These interactions suggest the compound’spotential antifungal and antibacterial activity, highlighting it as a promising scaffold forfurther medicinal chemistry exploration.