QSAR and molecular docking modelling of anti-leishmanial activities of organic selenium and tellurium compounds

Leishmaniasis affects mainly rural areas and the poorest people in the world. A computational study of the antileishmanial activity of organic selenium and tellurium compounds was performed. The 3D structures of the compounds were optimized at the wb97xd/lanl2dz level and used in the quantitative structure-activity relationship (QSAR) analysis. The antileishmanial activity was measured by L. donovani β carbonic anhydrase inhibition (Ki) and the half-maximal inhibitory concentration (IC₅₀) against L. infantum amastigotes. The dataset was divided into training (75%) and test sets (25%) by using a k-means clustering algorithm. For pKi prediction, model M3 with seven 3D topographic descriptors was characterized by the following statistical parameters: r ² = 0.879, Q ²_LOO = 0.822, and Q ²_ext = 0.840. For pIC₅₀ prediction, model M12 with six attributes was characterized by the following statistical parameters: r ² = 0.907, Q ²_LOO = 0.824, and Q ²_ext = 0.795. Both models met all the requirements of Tropsha´s test, which implies predictions of pIC₅₀ and pKi activities with high accuracy. Concomitantly, favourable interactions of the sulphonamide group with the Zn atom in the protein were revealed by the docking analysis.