Predictive Modeling of Toxoplasma Gondii Activity of a Series of Substituted Imidazole-Thiosemicarbazides Using Quantum Descriptors

Sopi Thomas Affi^{1, 2}, Bafétigué Ouattara³, Georges Stéphane Dembélé^{1, 2}, Mamadou Guy-Richard Koné^{1, 2,} and Nahossé Ziao^{1, 2}

¹Laboratoire de Thermodynamique et de Physico-Chimie du Milieu, UFR SFA, Université NANGUI ABROGOUA, 02 BP 801 Abidjan 02, Côte-d’Ivoire

²Groupe Ivoirien de Recherches en Modélisation des Maladies (GIR2M)

³Laboratoire de Physique Fondamentale et Appliquée, UFR SFA, Université NANGUI ABROGOUA, 02 BP 801 Abidjan 02, Côte-d’Ivoire

Cite this paper:
Sopi Thomas Affi, Bafétigué Ouattara, Georges Stéphane Dembélé, Mamadou Guy-Richard Koné and Nahossé Ziao. Predictive Modeling of Toxoplasma Gondii Activity of a Series of Substituted Imidazole-Thiosemicarbazides Using Quantum Descriptors. Physics and Materials Chemistry. 2021; 7(1):1-13. doi: 10.12691/pmc-7-1-1

Abstract

Quantitative Structure Activity Relationship (QSAR) study of Toxoplasma gondii was done on a series of twenty-five (25) imidazole-thiosemicarbazide molecules. In order to obtain molecular descriptors all these molecules were optimized at B3LYP/LanL2DZ level. This study was performed using the linear multiple regression (MLR), nonlinear regression (MNLR) and artificial neural network (ANN) methods. These statistical methods allow to find three (3) quantitative models. Quantum descriptors which such as energy gap (ΔE), dipole moment (μ), enthalpy of formation (ΔfH), bond length (D(C-S)) and lipophilicity (Logp) were used in models elaboration. Among obtained models, RNA model has much better predictive ability than other models with R² = 0.9291 and RMCE = 0.00023. A decrease in energy gap (ΔE) which is the main descriptor could significantly improve the Toxoplasma gondii IC₅₀ inhibitory concentration of substituted imidazole-thiosemicarbazide analogues. Furthermore, the external validation test pIC₅₀ theo/ pIC₅₀ exp and the applicability domain from Cook's distance were verified.

Keywords:
QSAR RNA Energy gap (ΔE) Toxoplasma gondii activity

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