Title: De novo design and pharmacophore prediction of AADC (aromatic L-amino acid decarboxylase) inhibitors

Authors: J. Jayanthi, V. Usha

Addresses: Sai's BioSciences Research Institute Pvt. Ltd., No. 144, 3rd Floor, Nelson Manickam Road, Chennai – 600 029 Tamil Nadu, India. ' Sai's BioSciences Research Institute Pvt. Ltd., No. 144, 3rd Floor, Nelson Manickam Road, Chennai – 600 029 Tamil Nadu, India

Abstract: AADC (Aromatic L-amino acid decarboxylase) is a lyase enzyme. It is a well known potential drug target for neurological disorders. Selective AADC inhibitors are used in the treatment of neurological disorders such as Parkinson|s. The aim of this work is to develop specific inhibitors, which may overcome the side effects that the existing inhibitors suffer from. In the light of these facts, AADC enzyme has been modelled and ligands have been generated from AADC enzyme with its known binding site using LUDI. Also, binding affinity of the ligand towards the enzyme has been enhanced. The number of ligands was selected based on the intermolecular h-bonds with receptor, polar surface area, molecular volume, Lipinski|s rule of five and docking studies. Finally, pharmacophoric features present in the selected ligands were predicted.

Keywords: aromatic L-amino acid decarboxylase; AADC inhibitors; LUDI; pharmacophore; lyase enzymes; drug targets; neurological disorders; pharmacophoric features; ligands.

DOI: 10.1504/IJMEI.2008.019471

International Journal of Medical Engineering and Informatics, 2008 Vol.1 No.1, pp.73 - 84

Published online: 13 Jul 2008 *

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