Molecular Docking and ADMET Profiling of Natural Compounds Targeting SIRT1/SIRT3 for Anti Aging Intervention

Abstract

Background: Sirtuin 1 (SIRT1) and sirtuin 3 (SIRT3) are NAD⁺-dependent deacylases that play critical roles in metabolic regulation, oxidative stress control, and aging. Natural products have emerged as promising sources of sirtuin-interacting molecules, yet systematic evaluation of Hyptis verticillata phytochemicals against these targets remains limited.
Methods: Selected phytochemicals from Hyptis verticillata were subjected to molecular docking against SIRT1 (PDB ID: 4I5I) and SIRT3 (PDB ID: 3GLS) using AutoDock Vina. Binding affinities and interaction patterns were analyzed, followed by in silico pharmacokinetic and toxicity (ADMET) profiling using SwissADME and admetSAR to assess drug-likeness and safety.
Results: Docking analysis revealed binding energies ranging from −5.0 to −9.5 kcal/mol across both targets. Squalene exhibited the strongest predicted affinity for SIRT1 (−9.5 kcal/mol), while oleanolic acid showed the highest affinity for SIRT3 (−8.5 kcal/mol). Several other compounds demonstrated moderate binding to both sirtuins. Interaction analysis indicated predominantly hydrophobic stabilization within the binding pockets. ADMET profiling suggested that while highly lipophilic compounds may face bioavailability limitations, oleanolic acid displayed a comparatively balanced pharmacokinetic and safety profile.
Conclusion: The findings indicate that selected H. verticillata phytochemicals exhibit structural compatibility with SIRT1 and SIRT3, supporting their consideration as preliminary sirtuin-interacting candidates. However, the results represent structure-based predictions rather than functional evidence. Further molecular dynamics simulations and experimental validation are required to elucidate binding stability and biological activity.