Theoretical Evaluation and Classifications of Potential Antimalarial Phenazine Compounds

Tania      M.B. e Silva; Nely      T.V. Cerqueira; Sheyla      W.D. Silva; Felipe      de M. Santos; Terezinha      F. Oliveira; Roberta      L. Ziolli; Carlton      A. Taft

Abstract

This study demonstrates a methodology for evaluating the theoretical antimalarial potential of 18 phenazine derivatives, some of which have no known biological activities. Semi-empirical, density functional and statistical methods for analytical data treatment were used to establish a quantitative structure-activity relationship (QSAR). A set of 16 descriptors were obtained. Theoretical tools regarding inferential statistics were used to analyze and interpret the information necessary for the application of a multivariate analysis. We classified four types of phenazines into distinct clusters taking into account including planarity, ring-attached substituents, geometric arrangement and conjugation effects, energy maps as well as frontier orbitals energies. The experimental data and crystallochemical analysis obtained in the present study were able to substantiate the chemo-theoretical analysis. Our classifications agree well with experimental evidence regarding compounds that have already been studied. it would also be desirable to conduct new experimental studies in order to further evaluate the predicting capability of our calculations.

Keywords: Chemometric, DFT, malaria, phenazines, antimalarial properties, antibiotic, griseolutein, molecules, biological activity, stereochemistry