Synthesis, Structural Elucidation and DFT studies of Novel Coumarin derivative with Docking, ADMET analysis and Antibacterial activities

In this study, we have synthesised a novel coumarin derivative via a nucleophilic substitution reaction between 7-amino-4-(trifluoromethyl)coumarin and acyl chlorides. The compound was characterised by NMR (1H and 13C) and FTIR spectroscopy, with structures validated by single-crystal X-ray diffraction. The compound crystallised in the monoclinic crystal system, space group P21/c. Crystal structure and Hirshfeld surface analyses revealed intermolecular C–H···O and N–H···O hydrogen bonds that stabilise the crystal structure, forming \(\:{R}_{2}^{1}\)(6) and \(\:{R}_{2}^{1}\)(7) supramolecular synthons. The geometrical coordinates of the compound was optimised using density functional theory (B3LYP/6-311 + G(d,p)), and, based on the optimised structure, various electronic properties were evaluated. The natural bond orbital (NBO) and quantum theory of atoms in molecule (QTAIM) analyses provided in-depth insights into the interactions exhibited by the compound. Molecular docking studies with protein [PDB:1AE1] demonstrated that the molecule exhibited strong binding affinity, highlighting its potential as an antibacterial agent. ADMET analysis revealed that drug can be orally active. The potential antibacterial activity of the synthesised compound was tested in vitro against 4 selected bacterial strains: Staphylococcus aureus (Gram-positive) and Bacillus subtilis (Gram-positive), and Escherichia coli and Klebsiella pneumonia (Gram-negative). The coumarin derivative showed potential antibacterial activity against the tested bacterial species.