Isolation of Phytochemicals from Calophyllum nodosum and In Silico Evaluation of Their Drug-Likeness and DNA Gyrase Inhibition Potential

Abstract

The Calophyllum species have gained a lot of attention for their structurally diverse secondary metabolites with potential biological activities, including antibacterial scaffolds. A detailed study done on the phytochemical profile of the Calophyllum nodosum stem bark has led to the isolation of three xanthones, trapezifolixanthone (1), caloxanthone C (2), 1-hydroxy-7-methoxyxanthone (3), and a cyclic ester, canumolactone (4). Their structures were characterised using spectroscopic techniques like NMR, MS, and IR, and the spectra were confirmed with the previous literature. The pharmacokinetic properties of the compounds were predicted using SwissADME and cross-validated using pkCSM, while molecular docking simulation against bacterial DNA gyrase was performed using Autodock Vina. All isolated compounds met the drug-likeness requirements under Lipinski’s rule, according to the ADMET predictions, showing favourable oral and gastrointestinal bioavailability and absorption. Canumolactone (4), in particular, showed the best combination of solubility, clearance, and the least amount of CYP liabilities. The molecular docking simulation revealed that trapezifolixanthone (1) gave the strongest binding affinity to DNA gyrase among all isolated compounds, surpassing the binding affinity of the standard inhibitor, BDBM50198240. The current study presents the first combined ADMET predictions and molecular docking analysis for compounds isolated from C. nodosum. The findings provide preliminary evidence of their potential as drug-like scaffolds for future pharmacological development.