Application of QSAR Method in the Design of Enhanced Antimalarial Derivatives of ...

The resistance of the P. falciparum strain to some of the antimalarial drugs has been a dominant dilemma facing the treatment of this fetid disease. This necessitates the detection and development of new antimalarial agents targeting the P. falciparum. Azetidine-2-carbonitriles reported for its antimalarial activities, could provide an alternative to the customized antimalarial drugs. Leading to the use of quantitative structure-activity relationship (QSAR) studies, which relates the structures of Azetidine-2-carbonitriles with their activities to generate predictive models. The structures were optimized using density functional theory (DFT) DFT/B3LYP/6-31G* basis set to generate their molecular descriptors, where five predictive models were constructed using the generated descriptors. The models were constructed using the genetic function algorithm component of a material studio, where the model with good statistical parameters, high coefficient of determination (R2) = 0.9465, cross-validated R2 (Q2cv) = 0.8981, Q2 (L4O)cv = 0.9272, and highest external validated R2 (R2pred) = 0.6915 was selected as the best model. These statistical results show the robustness, excellent power of prediction, and validity of the selected model. The descriptor, SpMax2_Bhp (the maximum absolute eigenvalue of Barysz matrix for n = 2 was weighted by polarizability), was revealed to be the most influential in the model due to its highest mean effect. The descriptor played a role in the design of s...
Source: Iranian Journal of Pharmaceutical Research - Category: Drugs & Pharmacology Source Type: research