International Journal of ChemTech Research CODEN( USA): IJCRGG ISSN : 0974-4290 Vol.2, No.2, pp 932-936, April-June 2010 Molecular Docking Studies of Some Novel Hydroxamic Acid Derivatives Supriyo Saha 1* , Subhasis Banerjee 1 and Swastika Ganguly 2 1 Department of Pharmaceutical Chemistry, Gupta college of Technological Sciences, Asharm More, Asansol-01, West Bengal, India. 2 Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi- (Jharkhand)-835215, India. * Corres.author: sups_3333@yahoo.co.in . Telephone no: 09333257220 Abstract: A series of few triazole linked hydroxamic acid derivatives were designed virtually considering the basic pharmacophore of suberoyl anilide hydroxamic acid (SAHA). The least energy conformers of each molecule was generated and docked with human histone deacetylase (HDAC8) with PDB id 1T69 using Autodock 4.0.1. Most of the molecules have shown significant binding interaction with the receptor. Among the test compounds, 1a and 1g have shown highest free energy of binding -7.04 kcal/mol and -7.23 kcal/mol respectively, which is comparable to that of the reference standard, SAHA. Keywords: Docking, Triazoles, SAHA, HDAC8. INTRODUCTION For the last four decades, a number of potential approaches have been proposed for the treatment of cancer. One of the recent targets is Histone deacetylase (HDAC). Modification of histone acetylation level, promoted by HAT and HDAC enzymes, has been recognized to play an important role in the epigenetic modulation of gene expression; in fact this well-known post-translational mechanism is highly involved in the modulation of chromatin plasticity and in the regulation of transcriptional factors accessibility to DNA; 1 therefore the disruption of histone acetylation pattern is supposed to determine transcriptional disorders and is related to several malignant diseases. 2 Inhibition of HDAC enzyme has proven to induce antiproliferative effects and to promote cellular differentiation. For these reasons, discovery of new agents targeting HDAC enzyme is considered of great interest for the development of anticancer drugs. 3,4 In recent years, hydroxamic acid derivatives have attracted increasing attention for their potential as highly efficacious in combating various etiological factors associated with cancer. Some of the HDAC inhibitors in clinical phases are Panobinostat 5 which is under investigation for various cancers including cutaneous T cell lymphoma (CTCL), Vorinostat 6 was licensed by the U.S. Food and Drug Administration in October 2006 for the treatment of CTCL, Romidepsin 7 is undergoing clinical trials as a treatment for cutaneous T-cell lymphoma (CTCL).Virtual screening requires a prerequisite knowledge about spatial and energetic criterion responsible for binding of particular candidate ligand (various hydroxamic acid derivatives) to the receptor (HDAC8) under investigation. In view of these facts, we wish to report the docking studies of some newly designed hydroxamic acid derivatives with HDAC8.