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

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), fo...

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Main Authors: Berin Karaman, Zayan Alhalabi, Sören Swyter, Shetonde O. Mihigo, Kerstin Andrae-Marobela, Manfred Jung, Wolfgang Sippl, Fidele Ntie-Kang
Format: Article
Language:English
Published: MDPI AG 2018-02-01
Series:Molecules
Subjects:
Online Access:http://www.mdpi.com/1420-3049/23/2/416
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author Berin Karaman
Zayan Alhalabi
Sören Swyter
Shetonde O. Mihigo
Kerstin Andrae-Marobela
Manfred Jung
Wolfgang Sippl
Fidele Ntie-Kang
author_facet Berin Karaman
Zayan Alhalabi
Sören Swyter
Shetonde O. Mihigo
Kerstin Andrae-Marobela
Manfred Jung
Wolfgang Sippl
Fidele Ntie-Kang
author_sort Berin Karaman
collection DOAJ
description 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.
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spelling doaj.art-299266acd5114615ba1c1fdeed08e6412022-12-21T18:26:33ZengMDPI AGMolecules1420-30492018-02-0123241610.3390/molecules23020416molecules23020416Identification of Bichalcones as Sirtuin Inhibitors by Virtual Screening and In Vitro TestingBerin Karaman0Zayan Alhalabi1Sören Swyter2Shetonde O. Mihigo3Kerstin Andrae-Marobela4Manfred Jung5Wolfgang Sippl6Fidele Ntie-Kang7Department of Pharmaceutical Chemistry, Martin-Luther University of Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle (Saale), GermanyDepartment of Pharmaceutical Chemistry, Martin-Luther University of Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle (Saale), GermanyInstitute of Pharmaceutical Sciences, Albert-Ludwigs-University of Freiburg, Albertstr. 25, 79104 Freiburg im Breisgau, GermanyDepartment of Chemistry, University of Kinshasa, Kinshasa P.O. Box 190 XI, CongoDepartment of Biological Sciences, Faculty of Science, University of Botswana, Block 235, Private Bag, Gaborone 0022, BotswanaInstitute of Pharmaceutical Sciences, Albert-Ludwigs-University of Freiburg, Albertstr. 25, 79104 Freiburg im Breisgau, GermanyDepartment of Pharmaceutical Chemistry, Martin-Luther University of Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle (Saale), GermanyDepartment of Pharmaceutical Chemistry, Martin-Luther University of Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle (Saale), GermanySirtuins 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.http://www.mdpi.com/1420-3049/23/2/416bichalconessirtuin inhibitorsvirtual screening
spellingShingle Berin Karaman
Zayan Alhalabi
Sören Swyter
Shetonde O. Mihigo
Kerstin Andrae-Marobela
Manfred Jung
Wolfgang Sippl
Fidele Ntie-Kang
Identification of Bichalcones as Sirtuin Inhibitors by Virtual Screening and In Vitro Testing
Molecules
bichalcones
sirtuin inhibitors
virtual screening
title Identification of Bichalcones as Sirtuin Inhibitors by Virtual Screening and In Vitro Testing
title_full Identification of Bichalcones as Sirtuin Inhibitors by Virtual Screening and In Vitro Testing
title_fullStr Identification of Bichalcones as Sirtuin Inhibitors by Virtual Screening and In Vitro Testing
title_full_unstemmed Identification of Bichalcones as Sirtuin Inhibitors by Virtual Screening and In Vitro Testing
title_short Identification of Bichalcones as Sirtuin Inhibitors by Virtual Screening and In Vitro Testing
title_sort identification of bichalcones as sirtuin inhibitors by virtual screening and in vitro testing
topic bichalcones
sirtuin inhibitors
virtual screening
url http://www.mdpi.com/1420-3049/23/2/416
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