Histone deacetylase inhibition activity of resveratrol and its analogs

MEDI 333

Didem Dayangac-Erden, didayan@hacettepe.edu.tr1, Peruze Ayhan, payhan@metu.edu.tr2, Gamze Bora, gamzeb@hacettepe.edu.tr1, Kemal Yelekci, yelekci@khas.edu.tr3, Sevim Dalkara, sdalkara@hacettepe.edu.tr4, Ayhan S. Demir, asdemir@metu.edu.tr2, and Hayat Erdem-Yurter, herdem@hacettepe.edu.tr1. (1) Department of Medical Biology, Hacettepe University Faculty of Medicine, Sihhiye, 06100 Ankara, Turkey, (2) Department of Chemistry, Middle East Technical University, Inonu Bulvari, 06531 Ankara, Turkey, (3) Faculty of Arts and Sciences, Kadir Has University, Fatih 34230, Istanbul, Turkey, (4) Department of Pharmaceutical Chemistry, Hacettepe University Faculty of Pharmacy, Sihhiye, 06100 Ankara, Turkey
Histone deacetylases (HDAC) are enzymes that play an important role in modifying chromatin structure and regulating gene expression. A number of HDAC inhibitors have been developed as anti-cancer agents. Resveratrol which is a molecule produced by plants in response to stress, is known to have anti-inflammatory, antioxidant and anti-cancer effects. In this preliminary study, HDAC inhibition activities of resveratrol and its analogues were investigated in vitro by using HeLa nuclear extract in a fluorimetric assay. High HDAC inhibitory activity was found in resveratrol in a concentration dependent manner. It showed more inhibitory effect than known HDAC inhibitors like short chain fatty acids. To display inhibitor positioning in the active site of HDAC enzyme, molecular docking studies were performed and results showed that resveratrol had the most favorable free energy of binding and inhibition constant values. Demonstration of HDAC inhibitory effect of resveratrol will provide new insights into pharmaceutical applications.
 

Poster Session
7:00 PM-9:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Medicinal Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007