Pattern Recognition Techniques Applied to the Study of Leishmanial Glyceraldehyde-3-Phosphate Dehydrogenase Inhibition

Abstract

Chemometric pattern recognition techniques were employed in order to obtain Structure-Activity Relationship (SAR) models relating the structures of a series of adenosine compounds to the affinity for glyceraldehyde 3-phosphate dehydrogenase of Leishmania mexicana (LmGAPDH). A training set of 49 compounds was used to build the models and the best ones were obtained with one geometrical and four electronic descriptors. Classification models were externally validated by predictions for a test set of 14 compounds not used in the model building process. Results of good quality were obtained, as verified by the correct classifications achieved. Moreover, the results are in good agreement with previous SAR studies on these molecules, to such an extent that we can suggest that these findings may help in further investigations on ligands of LmGAPDH capable of improving treatment of leishmaniasis.

Three-dimensional structures in the design of therapeutics targeting parasitic protozoa: reflections on the past, present and future

“…The resultant structure showed interesting differences between trypanosomatid GAPDH and its human counterpart near the ribose ring of the cofactor NAD which were exploited for selective inhibitor design (Aronov et al, 1999;Bressi et al, 2000;Suresh et al, 2001). Structure-guided studies focusing on trypanosomatid glycosomal enzymes and receptors are still actively being pursued (Barros-Alvarez et al, 2014;Guido et al, 2009;Lozano et al, 2014).…”