Drug Designing: Open Access
Open Access

Design of HDAC2 inhibitors based on molecular modeling

9^th Annual Congress on Drug Design & Drug Formulation

October 19-20, 2017 Seoul, South Korea

Geetha Ramakrishnan

Sathyabama University, India

Posters & Accepted Abstracts: Drug Des

Abstract :

Identification of the lead compounds and lead optimization for the histone deacetylase-2 (HDAC2) inhibition evinced great interest in cancer drug development. HDAC2 belongs to Class I HDAC family and a promising target for inhibition in the treatment of various cancers, includes colon, gastric, cervical, prostate carcinoma, lung cancer, colorectal and hepatocellular carcinoma. In this work, we used pharmacophore, virtual screening and molecular docking to identify novel compounds for HDAC2 protein. We identified total 30 inhibitors from three databases (NCI, Maybridge and ZINC) and selected compounds were subjected to molecular dynamic studies to check the stability of the complex. Finally selected few compounds are chosen to serve as best HDAC2 inhibitors. Compound (S)-3-(1-benzyl-1H-imidazol-4-yl)-2-[((benzyloxy) carbonyl) amino] propanoic acid (NSC169121 OR Z-His(Bzl)-OH) was chosen for experimental antioxidant and anticancer studies. Antioxidant property of compound measured using DPPH free radical assay and the cytotoxicity of the compound measured in three human cancer cell lines such as human lung carcinoma cells, human breast carcinoma cells and prostate carcinoma cells using MTT (3-[4,5-dimethylthiazol-2-yl] 2,5-diphenyl tetrazolium bromide) assay. The IC50 of the compound measured and the activity of the compound is increased by combination of quercetin and antioxidant. This study successfully finds potential novel compounds for HDAC2 inhibition and in vitro antioxidant and anticancer study of selected compound was found to have a reasonable IC50 value and the activity of the compound was enhanced by addition of quercetin.