Identification of Bichalcones as Sirtuin Inhibitors by Virtual Screening and In Vitro Testing

Abstract

Sirtuins are nicotinamide adenine dinucleotide (NAD⁺)-dependent class III histone deacetylases, which have been linked to the pathogenesis of numerous diseases, including HIV, metabolic disorders, neurodegeneration and cancer. Docking of the virtual pan-African natural products library (p-ANAPL), followed by in vitro testing, resulted in the identification of two inhibitors of sirtuin 1, 2 and 3 (sirt1-3). Two bichalcones, known as rhuschalcone IV (<b>8</b>) and an analogue of rhuschalcone I (<b>9</b>), previously isolated from the medicinal plant <i>Rhus pyroides</i>, were shown to be active in the in vitro assay. The rhuschalcone I analogue (<b>9</b>) showed the best activity against sirt1, with an IC₅₀ value of 40.8 µM. Based on the docking experiments, suggestions for improving the biological activities of the newly identified hit compounds have been provided.