Computational Evaluation of Solanum Nigrum Phytochemicals for Dermatophyte Inhibition: ADMET, Docking, and Molecular Dynamics Studies

Abstract

Purpose

Dermatophytosis, a widespread superficial fungal infection affecting nearly a quarter of the global population, presents growing therapeutic challenges due to emerging resistance and tolerance among dermatophyte strains. This study investigates the antifungal potential of phytoconstituents from Solanum nigrum Linn. berries against dermatophytid strains using In-silico methods.

Method

Ten bioactive compounds—solanine, solasodine, apigenin, catechin, p-coumaric acid, epicatechin, kaempferol, quercetin, rutin, and luteolin—were systematically assessed for drug-likeness, ADMET (absorption, distribution, metabolism, excretion and toxicity) properties, molecular docking, and dynamic simulation. Key fungal protein targets (2CG9, 4QUV, and 5UIV) were selected to evaluate binding efficacy.

Results

Most compounds exhibited favourable drug-like properties, with molecular weights ranging from 172.224 to 413.646 Da and log P values below 5. ADMET analysis revealed moderate to low water solubility, favourable intestinal absorption, and low skin permeability. None of the compounds were found to cross the blood-brain barrier or inhibit P-glycoprotein I/II. Toxicity predictions indicated no AMES toxicity, hepatotoxicity, or skin sensitization. Molecular docking studies against protein targets 2CG9, 4QUV, and 5UIV showed notable binding affinities for all compounds, with solanine and solasodine demonstrating the highest binding scores. Molecular dynamics simulations of solanine and solasodine with 5UIV revealed stable interactions and structural integrity of the protein-ligand complexes.

Conclusion

These findings highlight the potential of solanine and solasodine as effective modulators of dermatophytid strains, warranting further experimental validation. This study provides valuable insights into the antifungal activity of Solanum nigrum Linn. berry phytoconstituents and their potential as novel therapeutic agents against dermatophytosis.