In Vitro and In Silico Structure-Based Discovery of Furan-Chalcones as Potent Urease Inhibitors: Insights from Molecular Docking, Structure-Activity Relationship, Molecular Dynamics Simulations, ADME, and DFT Studies

Furan-chalcones are privileged and promising heterocyclic compounds that display a broad spectrum of biomedical applications in fields such as medicine, pharmacology, pharmaceutics, and pharmaceuticals. The microwave-assisted furan-chalcone molecules (18) were synthesized and obtained in excellent yields (80–90%) in comparison to the conventional synthetic approach (65–80%). These furan-chalcone derivatives were evaluated as urease inhibitors by using the jack bean urease enzyme. Among the all-screened compounds, 4-nitrophenyl and 2,5-dinitrophenyl-containing furan-chalcone 5o (IC[Formula: see text] 14.83 ± 3.67 [Formula: see text]M) and 4-nitrophenyl and 2-chloro-4-nitrophenyl-based furan-chalcone 5q (IC[Formula: see text] 18.94 ± 2.05 [Formula: see text]M) exhibited excellent in vitro urease inhibition activity compared to the reference urease inhibitory drug thiourea (IC[Formula: see text] 21.25 ± 0.15 [Formula: see text]M). The synthesized compounds (5a–5r) are simulated at the DFT/B3LYP/6-311G(d,p) theory level to optimize the geometries of the compounds under study. Then electronic properties such as frontier molecular orbital (FMO), molecular electrostatic potential (MEP), dipole moment, polarizability, and global reactivity features are calculated at the same theoretical level.In silico molecular docking and molecular dynamic (MD) simulation and density functional theory (DFT) studies results are in agreement with in vitro findings. The ADMET study results displayed that these most bio-potent furan-chalcone compounds exhibited good pharmacokinetic and drug-likeness profiles. According to structure–activity relationship (SAR), molecular docking, MD simulations, and ADMET studies, furan-chalcone compounds 5o and 5q may serve as potential leads as urease inhibitors. The outcomes of the current study hold significant and substantial therapeutic potential for advancing future drug development of effective urease inhibitors from this bio-potent furan-chalcone class.