Quantitative Structure-Activity Study against Plasmodium falciparum of a Series of Derivatives of Azetidine-2-Carbonitriles by the Method of Density Functional Theory

Abstract

<p>This work deals with a Quantitative Structure-Activity study against <em>Plasmodium</em> <em>falciparum</em> of a series of Azetidine-2-carbonitrile derivatives. Using the MLR and MNLR methods from excel and xlstat software, we have been able to develop two QSAR models based on molecular descriptors and plasmodial activity. Calculation level B3LYP/6-311 G (d, p) was used to determine molecular descriptors. The statistical indicators of the first model obtained by the MLR method are: the regression coefficient found was <strong>R<sup>2</sup></strong> = 0.939 with a standard deviation S =0.266, Fischer's coefficient F =82.064, and a cross-validation correlation coefficient =0.935. The parameters of the second model developed by the MNLR method are: the regression coefficient <strong>R<sup>2</sup></strong>: de 0.953, a standard deviation S of 0.258, the Fischer's test F of 108.957, and the correlation coefficient of the cross-validation =0.951. Moreover, these models have shown some interesting statistical performance. The energy of the highest occupied molecular orbital (E<sub>HOMO</sub>), the dipole moment (µD), and the partition coefficient (log P) are the molecular descriptors responsible for the <em>Plasmodium falciparum</em> activity of Azetidine-derivatives 2-carbonitriles. Furthermore, the partition coefficient is the primary descriptor for predicting the biological activity of the studied compounds. From the findings, Eriksson <em>et al.</em> and the external validation criteria of Tropsha used to implement the test are verified and accurate.</p>