DFT Based QSAR Study of Enzyme Ribonucleoside Diphosphate Reductase

Mohiuddin Ansari,Ahmad Khalid Raza Khan ,Suhail Ahmad Khan

doi:10.1155/2010/254539

Abstract

Quantum chemical descriptors such as heat of formation, energy of HOMO, total energy, absolute hardness and chemical potential in different combinations have been used to develop QSAR models of inhibitors of enzyme ribonucleoside diphosphate reductase, RDR. The inhibitors are mainly derivatives of 1-formylisoquinoline thiosemicarbazone and 2-formylpyridine thiosemicarbazone. The values of various descriptors have been evaluated with the help of Win MOPAC 7.21 software using DFT method. Multiple linear regression analysis has been made with the help of above mentioned descriptors using the same software. Regression equations have been found to be successful models as indicated by the regression coefficientr2having the value as high as 0.96 and cross validation coefficientrCV2having the value approaching 0.95. The value of these two coefficients is indicative of high order of reliability for the proposed prediction. The results obtained are also validated on account of the closeness of observed and predicted inhibitory activities. The best combination of descriptors is heat of formation, total energy and energy of HOMO. Thus the prediction of suitability of inhibitors of the enzyme RDR can be made with the help of the best regression equation.

Highlights

Quantitative Structure Activity Relationship, QSAR, a quantum chemical technique[1,2,3] is known to relate the biological activity of compounds with their molecular structure[4] and has been extensively used as predicting tool in rational drug design[5,6,7,8,9,10]
2-Formylpyridine thiosemicarbazone derivatives have been divided into two different sets on the basis of difference in the position of substituents
The QSAR model of four sets of derivatives of thiosemicabazone has been developed with reliable predictive power

Summary

Introduction

Quantitative Structure Activity Relationship, QSAR, a quantum chemical technique[1,2,3] is known to relate the biological activity of compounds with their molecular structure[4] and has been extensively used as predicting tool in rational drug design[5,6,7,8,9,10]. QSAR study of inhibitory activity of 30 derivatives of 2-formylpyridine thiosemicarbazone and 21 derivatives of 1-formylisoquinoline thiosemicarbazone with the help of new set of descriptors; heat of formation[19], eigen value of highest occupied molecular orbital[20], eigen value of lowest unoccupied molecular orbital[21], total energy[22], absolute hardness[23,24] and chemical potential[25] against the enzyme, RDR, have been made in this paper. These descriptors have been successfully employed for QSAR study recently[8].

Results and Discussion

20 NHCOCH3

Conclusion