Identification of Bichalcones as Sirtuin Inhibitors by Virtual Screening and In Vitro Testing.
Berin KaramanZayan AlhalabiSören SwyterShetonde O MihigoKerstin Andrae-MarobelaManfred JungWolfgang SipplFidele Ntie-KangPublished in: Molecules (Basel, Switzerland) (2018)
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 improving the biological activities of the newly identified hit compounds have been provided.
Keyphrases
- molecular dynamics
- molecular dynamics simulations
- protein protein
- oxidative stress
- antiretroviral therapy
- hiv positive
- papillary thyroid
- bioinformatics analysis
- hiv infected
- ischemia reperfusion injury
- human immunodeficiency virus
- hepatitis c virus
- dna methylation
- high throughput
- men who have sex with men
- south africa
- lymph node metastasis
- virtual reality