MODELING OF CARBONIC ANHYDRASE (II) INHIBITORY ACTIVITIES OF SULPHONILAMIDE SCHIFF BASES BY ARTIFICIAL NEURAL NETWORK TRAINED WITH DIFFERENT NUMERICAL TECHNIQUES

Vandana Pandey

doi:10.22159/ijpps.2018v10i1.22775

Abstract

Objective: The aim of the present study was to develop robust linear and non-linear Quantitative Structure-Activity Relationship (QSAR) models for exploring the relationship between the structural features of a series of sulphanilamide Schiff bases and their CA (II) inhibition activities.Methods: QSAR modeling of carbonic anhydrase (II) inhibiting activities of a series of sulphanilamide Schiff bases as a function of theoretically derived molecular descriptors calculated by Dragon software was established linearly by stepwise multiple linear regression (SW-MLR) method and non-linearly by artificial neural network (ANN) method, trained with different numerical techniques namely, Scaled conjugate gradient (SCG), quasi-Newton (BFGS), and Levenberg-Marquardt (LM) algorithm. SW-MLR method was also used to select descriptors from large descriptor pool. After the selection of variables, best selected linear model was validated by Y-randomization test. The applicability domain was assessed by the normalized mean Euclidean distance value for each compound. The prediction quality of proposed non-linear QSAR models was tested externally using validation and test set.Results: The low value of R2average = 0.214 from the Y-randomization test and no significant correlation between the selected descriptors indicates that linear model is reliable, and robust. Applicability domain analysis has also revealed that the suggested model has acceptable predictability. To explore non-linear relationship between selected descriptors and the target property, ANN approach trained with three supervised algorithms (BFGS, SCG and LM) was used. Statistical comparison of the quality of models obtained using ANN method trained with above mentioned three algorithms with SW-MLR model shows that ANN with 4-3-1 architecture and trained with LM algorithm has better predictive power as indicated by low RMSEval (0.11), MAPEval (11.95) values and high R2val (0.96) value.Conclusion: The results of this work indicated the ANN trained with fastest Levenberg-Marqardt algorithm is a promising tool for establishing non-linear relationship between selected sulphanilamide Schiffbases and their CA (II) inhibition values.

Highlights

Carbonic anhydrases (CAs) are a class of metalloenzymes containing Zn2+ion as active site
The reduced data set containing twenty-five descriptors was further subjected to stepwise regression analysis in order to select a limited number of descriptors significantly contributing to the prediction of logKCA (II) inhibitory activity of Schiff bases of sulfanilamides
GETAWAY descriptors are calculated from the leverage/geometry matrix obtained by centered atomic coordinates and Weighted Holistic Invariant molecular (WHIM) descriptors are geometrical descriptors based on statistical indices built to capture relevant 3D information regarding molecule

Summary

Introduction

Carbonic anhydrases (CAs) are a class of metalloenzymes containing Zn2+ion as active site. Role of QSAR in accessing and reducing risks for sustainable development is well documented [7, 8]. These models are mathematical equations constructing a relationship between theoretical descriptors [9] obtained from chemical structures and biological activities. Generalization, convergence and complexity are some of the important factors in training of a multilayer feed-forward artificial neural network which influence its performance. These factors are highly dependent upon the type of numerical technique or algorithm used for training

Methods

Results

Conclusion