QSAR Studies of Toxicity Towards Monocytes with (1,3-benzothiazol-2-yl) amino-9-(10H)-acridinone Derivatives Using Electronic Descriptors

Chtita Samir,Ghamali Mounir,Mohammed Bouachrine,Tahar Lakhlifi,Majdouline Larif

doi:10.17807/orbital.v7i2.677

Chtita Samir, Ghamali Mounir + Show 3 more

Open Access

https://doi.org/10.17807/orbital.v7i2.677

Copy DOI

Abstract

DFT-B3LYP method, with the basis set 6-31G (d), was employed to calculate nine quantum chemical descriptors of 16 acridin-9-(10H)-ones substituted with amino or (1,3-benzothiazol-2-yl)-amino groups compounds. The above descriptors were used to establish a Quantitative Structure Activity Relationship (QSAR) of the Anti-proliferative towards human monocytes activity of these compounds by Multiple Linear Regression (MLR), Multiple Non Linear Regression (MNLR) and Artificial Neural Network (ANN). The statistical results indicate that the correlation coefficients R were 0.864, 0.908 and 0.844 respectively. Results showed that the three modeling methods can provide a good prediction of the studied activity and may be useful for predicting the bioactivity of new compounds of similar class, and showed that the Multiple Non Linear Regression (MNLR) results have substantially better predictive capability than the MLR and ANN. The statistical results indicate that the models are statistically significant and show very good stability towards data variation in leave one out cross validation. DOI: http://dx.doi.org/10.17807/orbital.v7i2.677

Highlights

Acridines family includes a wide range of tricyclic molecules with various biological properties and consists of a nitrogen atom (N-atom) in its heterocyclic nucleus
- Three different modeling methods, multiple linear regression (MLR), Multiple Non Linear Regression (MNLR) and artificial neural network (ANN) were used in the construction of a Quantitative Structure Activity Relationship (QSAR) model for the Anti-proliferative towards human monocytes activities with acridin-9-(10H)ones substituted with amino or (1,3-benzothiazol-2yl)-amino groups compounds and the resulting models were compared
- It was shown that the multiple regression non linear MNLR results have substantially better predictive capability than the MLR and ANN yields a regression model with improved predictive power

Summary

Introduction

Acridines family includes a wide range of tricyclic molecules with various biological properties and consists of a nitrogen atom (N-atom) in its heterocyclic nucleus. First employed as anti-bacterial agents during the beginning of the twentieth century [13], they have rapidly revealed interesting anti-proliferative activities against both protozoa and tumor cells [7,8]. As a consequence, they have been extensively used in anti-parasitic chemotherapy and a wide range of new numerous acridines derivatives have been synthesized and successfully assessed for their anti-leishmanial properties [1, 14]. Whether the activities can be predicted with satisfactory accuracy depends to a great extent on the performance of the applied multivariate data analysis method, provided the property being predicted is related to the

Objectives

Methods

Results

Conclusion