Application of Molecular Topology to the Analysis of Antimalarial Activity of 4-Aminobicyclo[2.2.2]Octan-2-yl 4-Aminobutanoate and their Equivalents Ethanoates and Propanoates

  • C. Otero-Pérez Departamento de Farmacia y Tecnología Farmacéutica y Parasitología. Facultad de Farmacia. Universitat de València.
  • I. Baptista-Peraza Departamento de Farmacia y Tecnología Farmacéutica y Parasitología. Facultad de Farmacia. Universitat de València.
  • S. González-Apráez Departamento de Farmacia y Tecnología Farmacéutica y Parasitología. Facultad de Farmacia. Universitat de València.
  • A. Pertegás-Sevilla Departamento de Farmacia y Tecnología Farmacéutica y Parasitología. Facultad de Farmacia. Universitat de València.
  • J. Gálvez Departamento de Química Física. Facultad de Farmacia. Universitat de València.
  • R. García-Domenech Departamento de Química Física. Facultad de Farmacia. Universitat de València.
Keywords: Molecular topology, QSAR, malaria, antimalarial drugs

Abstract

Malaria causes one of the highest mortality rates worldwide. Malaria cases and malaria deaths are still increasing due to, among other factors, the resistance that the parasite has developed to treatments. New molecules have been analyzed to be used as treatment for this disease. The present study predicts the antiplasmodial activity of the Aminobicyclo[2.2.2]octan-2-yl 4-aminobutanoates and their equivalents ethanoates and propanoates using molecular topology to develop a quantitative structure-activity relation (QSAR) model. Linear discriminant analysis was used to find a mathematical statement able to classify 32 of 35 compounds accurately by their antiplasmodial activity. The model classified 82.35 % of molecules considered active with experimental methods, and differentiated 100 % of the inactive molecules as such. Multilinear regression analysis was applied to find an equation with the ability to predict the antiplasmodial activity of each compound in terms of pIC50. Crossvalidation and randomness tests were carried out to validate this model. Finally, new potential antiplasmodial molecules have been proposed.

Keywords: Molecular topology, QSAR, malaria, antimalarial drugs.

Published
2019-06-03