In silico evaluation of geroprotective phytochemicals as potential sirtuin 1 interactors

Sirtuin 1 (SIRT1) belongs to the histone deacetylase enzyme family and its activity regulates various signaling networks associated with aging. SIRT1 is widely involved in a large number of biological processes, including senescence, autophagy, inflammation, and oxidative stress. In addition, SIRT1 activation may improve lifespan and health in numerous experimental models. Therefore, SIRT1 targeting is a potential strategy to delay or reverse aging and age-related diseases. Although SIRT1 is activated by a wide array of small molecules, only a limited number of phytochemicals that directly interact with SIRT1 have been identified. Using the Geroprotectors.org database and a literature search, the aim of this study was to identify geroprotective phytochemicals that might interact with SIRT1. We performed molecular docking, density functional theory studies, molecular dynamic simulations (MDS), and absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction to screen potential candidates against SIRT1. After the initial screening of 70 phytochemicals, crocin, celastrol, hesperidin, taxifolin, vitexin, and quercetin had significant binding affinity scores. These six compounds established multiple hydrogen-bonding and hydrophobic interactions with SIRT1 and showed good drug-likeness and ADMET properties. In particular, crocin was further analyzed using MDS to study its complex with SIRT1 during simulation. Crocin has a high reactivity to SIRT1 and can form a stable complex with it, showing a good ability to fit into the binding pocket. Although further investigations are required, our results suggest that these geroprotective phytochemicals, especially crocin, are novel interacting partners of SIRT1.