Computational Analysis of Antioxidant Effects on Stress Response Mechanisms in Candida albicans

Abstract

Candida albicans was used as a eukaryotic model to study aging and oxidative stress response pathways focused on NAD dependent deacetylases, Sir2 and SIRT3. A significant gene expression regulation of both Sir2 and SIRT3 was observed under sublethal hydrogen peroxide treatment towards their association with stress adaptation. Natural ligands known for antioxidant properties were docked against Sir2 and SIRT3 structures. Binding free energy of most components fall in the range of -5.0 to -11 kcal/mol. The best candidates pterostilbene, quercetin and naringenin formed stable hydrophobic interactions and hydrogen bonds within catalytic and NAD binding pockets confirmed by visualization. Detailed ADME profiling shows most of the ligands passed the Lipinski rule of five and revealed a very good gastrointestinal absorption. PASS (Prediction of Activity Spectra for Substances) and SOM (Sites of Metabolism) predicts antioxidants, anti-aging properties, toxicity profiles, with key metabolic hotspots. This integrated in-silico approach highlights naringenin and quercetin as promising modulators of Sir2/SIRT3 mediated metabolic pathways in Candida albicans, warranting further validation with the help of in-vitro and in-vivo methods.