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 (8) and an analogue of rhuschalcone I (9), previously isolated from the medicinal plant Rhus pyroides, were shown to be active in the in vitro assay. The rhuschalcone I analogue (9) showed the best activity against sirt1, with an IC₅₀ value of 40.8 µM. Based on the docking experiments, suggestions for improv

SUBMITTER: Karaman B 

PROVIDER: S-EPMC6017733 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature