Dietary Compound Resveratrol Is a Pan-BET Bromodomain Inhibitor

Autor(es)

Dutra, Luiz Antonio ^{[1, 2, 3]} ; Heidenreich, David ^{[2, 3]} ; Bernardes da Silva, Gabriel Dalio ^[1] ; Chin, Chung Man ^[1] ; Knapp, Stefan ^{[2, 3]} ; dos Santos, Jean Leandro ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, BR-14800903 Araraquara - Brazil

^[2] Goethe Univ, Inst Pharmaceut Chem, D-60438 Frankfurt - Germany

^[3] Goethe Univ, Buchmann Inst Life Sci, D-60438 Frankfurt - Germany

• Tipo de documento: Artigo Científico
• Fonte: NUTRIENTS; v. 9, n. 11 NOV 2017.
• Citações Web of Science: 6

Resumo

The chemopreventive and anticancer effects of resveratrol (RSV) are widely reported in the literature. Specifically, mechanisms involving epigenetic regulation are promising targets to regulate tumor development. Bromodomains act as epigenetic readers by recognizing lysine acetylation on histone tails and boosting gene expression in order to regulate tissue-specific transcription. In this work, we showed that RSV is a pan-BET inhibitor. Using Differential Scanning Fluorimetry (DSF), we showed that RSV at 100 mu M increased the melting temperature (Delta Tm) of BET bromodomains by around 2.0 degrees C. The micromolar dissociation constant (K-d) range was characterized using Isothermal Titration Calorimetry (ITC). The RSV K-d value accounted to 6.6 mu M in case of BRD4(1). Molecular docking proposed the binding mode of RSV against BRD4(1) mimicking the acetyl-lysine interactions. All these results suggest that RSV can also recognize epigenetic readers domains by interacting with BET bromodomains. (AU)

• Processo FAPESP: 15/19531-1 - Inibição de histona deacetilase (HDAC-1 e HDAC-2) como alvos para indução de Hemoglobina Fetal na Anemia Falciforme
• Beneficiário: Jean Leandro dos Santos
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/08880-8 - Síntese e avaliação farmacológica de inibidores de Bromodomínio-3 (BRD-3) planejados como indutores de hemoglobina fetal
• Beneficiário: Gabriel Dalio Bernardes da Silva
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 14/03945-9 - Planejamento, síntese e avaliação farmacológica de novos compostos derivados de resveratrol úteis ao tratamento da dislipidemia
• Beneficiário: Luiz Antonio Dutra
• Modalidade de apoio: Bolsas no Brasil - Doutorado