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Molecules 2018, 23(2), 416; https://doi.org/10.3390/molecules23020416

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

1
Department of Pharmaceutical Chemistry, Martin-Luther University of Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle (Saale), Germany
2
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Biruni University, Istanbul 34010, Turkey
3
Institute of Pharmaceutical Sciences, Albert-Ludwigs-University of Freiburg, Albertstr. 25, 79104 Freiburg im Breisgau, Germany
4
Department of Chemistry, University of Kinshasa, Kinshasa P.O. Box 190 XI, Congo
5
Department of Biological Sciences, Faculty of Science, University of Botswana, Block 235, Private Bag, Gaborone 0022, Botswana
6
Department of Chemistry, University of Buea, P.O. Box 63, Buea 00237, Cameroon
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 23 January 2018 / Revised: 9 February 2018 / Accepted: 10 February 2018 / Published: 14 February 2018
(This article belongs to the Special Issue Structure-Activity Relationship of Natural Products 2018)
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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 improving the biological activities of the newly identified hit compounds have been provided. View Full-Text
Keywords: bichalcones; sirtuin inhibitors; virtual screening bichalcones; sirtuin inhibitors; virtual screening
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Karaman, B.; Alhalabi, Z.; Swyter, S.; Mihigo, S.O.; Andrae-Marobela, K.; Jung, M.; Sippl, W.; Ntie-Kang, F. Identification of Bichalcones as Sirtuin Inhibitors by Virtual Screening and In Vitro Testing. Molecules 2018, 23, 416.

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