Synthesis, Characterization, and Computational Studies of Novel 5‐(Substituted)‐1,5‐Dihydro‐2 H ‐Chromeno2,3‐dPyrimidine‐2,4(3 H )‐Dione Scaffolds as Potent Biological Agents

ABSTRACT In this work, we report a novel series of 5‐(substituted)‐1,5‐dihydro‐2 H ‐chromeno2,3‐dpyrimidine‐2,4(3 H )‐dione derivatives 4(a–e) and 5(a–d) by a one‐pot three‐component reaction of barbituric/1,3‐dimethyl barbituric acid, substituted salicylaldehyde, and 4‐hydroxy‐6‐methyl‐2‐pyrone/2‐hydroxy‐1,4‐naphthoquinone. The structures of the target compounds were precisely established using different spectroscopic (FT‐IR, NMR, and HRMS) studies. Through density functional theory (DFT) analysis, geometrical optimization, frontier molecular orbitals, molecular electrostatic potential regions, and quantum chemical parameters were assessed to explore the electronic properties of the synthesized molecules. The synthesized compounds were screened for their efficacy in combating M. tuberculosis using the MABA assay; compounds 5(a–d) containing 2‐hydroxy‐1,4‐naphthoquinone exhibited excellent antitubercular potency with an MIC of 3.12 µg/mL. Additionally, target compounds were evaluated for their in vitro antimicrobial activity against a range of bacterial strains ( S. aureus , S. mutans , E. coli , and S. Typhi ) and a fungal strain ( A. niger ). Compounds 4c , 4d , 5a , and 5c exhibited significant antimicrobial activity against the tested pathogens. Further, in silico molecular docking analyses were conducted with the enoyl‐ACP reductase (InhA) receptor to elucidate the binding interactions of the target ligands; compounds 5a and 5c exhibited the highest docking scores of −11.0 kcal/mol within the active site of InhA.