Inhibition Studies of Pyrimidine Class of Compounds on Enoyl-Acp Reductase Enzyme

Sunil H Ganatra

doi:10.4172/jcsb.1000097

Abstract

Present work is aimed to identify and understand the inhibiting nature of Pyrimidine class of compounds to Enoyl acyl carrier proteinreductase (Enoyl-ACP reductase), which is one of the main receptor proteins used in drug discovery for screening anti-leprosy agents. Series of Pyrimidine based compounds virtually designed using the Molecular mechanic technique. The designed molecules were docked using with crystal structure of Enoyl-ACP reductase (PDB ID : 2NTV) using Autodock molecular docking software. The method uses rigid-protein and flexible ligand-techniques to acquire maximum conformations of ligand molecules. The docking results were evaluated using the acquired binding energy values for each ligand-protein complex. Those molecules having higher negative binding energy values with higher hydrogen bonds are selected for further analysis. The selected molecules show better hydrophobic, electrostatic and steric interactions with receptor protein. It is reported that the presence of –CH2OH at R1 and –C6H5 at R2 and R3 positions enhance the negative binding energy (âG kcal mol-1) values. Particularly –OC6H5 at R1and –OH at R2 help in increasing the interactions between ligand and protein. The results show the molecular level interactions and inhibit the receptor protein.

Highlights

Leprosy is a chronic disease caused by the bacteria Mycobacterium leprae and Mycobacterium lepromatosis
The ligand fitting into the active site and higher interactions depends on the binding energies and possibilities of number of hydrogen bonds
The docking results provide the possibilities of hydrogen bonds between the atoms of ligand and amino acids

Summary

Introduction

Leprosy is a chronic disease caused by the bacteria Mycobacterium leprae and Mycobacterium lepromatosis. The World health organization (WHO) reported that it is one of the major diseases in developing countries [3]. The disease has its presence in developing countries due to age old social stigma [4]. The effective treatment for the disease appeared in the year 1930s with the introduction of new drug Dapsone and its derivatives. Soon the bacteria develop resistance for the Dapsone and the treatment of Dapsone was turmoil. The medicine problems remained until the introduction of multi drug therapy (MDT) from 1980s. Though this treatment is effective but it is quite expensive. There is urgent need to find new anti-leprosy agents

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