In Silico Evaluation of Acalypha indica Phytochemicals as Potential Antifungal Agents Targeting Saccharomyces cerevisiae Lanosterol 14-Alpha Demethylase.

The rise in antifungal resistance underscores the need to explore novel bioactive compounds. This study investigates phytochemicals from Acalypha indica as potential inhibitors of lanosterol 14-alpha demethylase (CYP51) in Saccharomyces cerevisiae. A total of sixteen phytocompounds were evaluated using molecular docking, MM/GBSA binding free energy estimation, pharmacokinetic and toxicity predictions, and 200 ns molecular dynamics (MD) simulations. Among them, stigmasterol, aurantiamide, and beta-sitosterol showed strong binding affinities, comparable to standard drugs fluconazole and itraconazole. ADME analysis revealed good drug-likeness and gastrointestinal absorption for aurantiamide and 2-methylanthraquinone. ProTox-III predictions indicated low mutagenic and carcinogenic risks for most compounds, although aurantiamide may have nephrotoxic and respiratory toxicity concerns. Top ligands aurantiamide and stigmasterol were further subjected to MD simulations, which demonstrated stable RMSD, low RMSF, and well-maintained secondary structure, indicating strong interaction persistence and structural integrity. Ligand behaviour metrics (rGyr, SASA, MolSA, PSA, intra-HB) supported their binding stability. While aurantiamide exhibited an unfavourable binding energy (+228.37 kcal/mol), stigmasterol displayed a significantly favourable ΔG_bind (-93.36 kcal/mol). These findings suggest that stigmasterol and related phytochemicals hold promise as natural antifungal agents. However, further in vitro and in vivo validation, along with structure-activity relationship (SAR) optimization, is essential for clinical advancement.