Unlocking the anti-infective potential of phytoconstituents derived from Euphorbia neriifolia Linn.: Molecular docking, pharmacokinetics, drug-likeliness, and toxicological evaluations

Growing resistance to conventional antibiotics has promoted interest in bioactive molecules derived from plants that may have anti-infective effects. Euphorbia neriifolia has long been used for its therapeutic benefits, exhibited potential as a source of antimicrobial natural products . The present research aimed to investigate the molecular interactions of several lead compounds of E. neriifolia focusing on antimicrobial effects, pharmacokinetics and toxicological properties, including their drug-likeliness profiles. A total of 18 lead compounds of E. neriifolia were retrieved from the literature based on their antimicrobial properties. PyRx, PyMol, and Discovery Studio (v4.5) were used for molecular docking against CTX-M-9 Beta-lactamase, dihydrofolate reductase enzyme, DNA gyrase , and OmpF Porin for antibacterial properties; 3CL protease , RNA dependent RNA polymerase (RdRp), and spike protein for anti-SARS-CoV-2 potential; neuraminidase and hemagglutinin H1 for anti-influenza; old yellow enzyme for antifungal ; and HIV-1 reverse transcriptase for anti-HIV activities. Absorption, distribution, metabolism, excretion, and toxicity (ADME/T) with drug likeliness properties were analyzed using pkCSM and Swiss ADME online tools. Among the 18 compounds, rutin and tulipanian exhibited higher binding affinities against most targets than their corresponding standard ligands. Most compounds, including rutin, friedelin , lupenone, beta-amyrin, and tulipanin, showed OmpF Porin protein inhibitory properties. At least 10 compounds, including quercetin , rutin, tulipanin, afzelin, pachypodol, and euphonerin A-D, exhibited higher binding affinities against the fungal old yellow enzyme, revealing promising antifungal properties. Furthermore, most compounds exerted favorable ADME/T properties and showed drug likeliness by obeying the Lipinski rule of five . Based on the current findings, this study offers the possibility of making a natural remedy for treating microbial infections from E. neriifolia . These results can be considered as the groundwork for developing plant-based medicinal compounds and conducting further in silico and experimental validation.