Chemometric studies on natural products as potential inhibitors of the NADH oxidase from Trypanosoma cruzi using the VolSurf approach.
Natural products have widespread biological activities, including inhibition of mitochondrial enzyme systems. Some of these activities, for example cytotoxicity, may be the result of alteration of cellular bioenergetics. Based on previous computer-aided drug design (CADD) studies and considering reported data on structure-activity relationships (SAR), an assumption regarding the mechanism of action of natural products against parasitic infections involves the NADH-oxidase inhibition. In this study, chemometric tools, such as: Principal Component Analysis (PCA), Consensus PCA (CPCA), and partial least squares regression (PLS), were applied to a set of forty natural compounds, acting as NADH-oxidase inhibitors. The calculations were performed using the VolSurf+ program. The formalisms employed generated good exploratory and predictive results. The independent variables or descriptors having a hydrophobic profile were strongly correlated to the biological data.
Scotti
Luciana
L
LTF, University Federal of Paraíba, Campus I, João Pessoa-PB, Brazil.
Ferreira
Elizabeth Igne
EI
Silva
Marcelo Sobral da
MS
Scotti
Marcus Tullius
MT
D000818:Animals; D001688:Biological Products / Q000737:chemistry / Q000627:therapeutic use; D014355:Chagas Disease / Q000188:drug therapy; D005419:Flavonoids / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors*; D021281:Quantitative Structure-Activity Relationship; D014349:Trypanosoma cruzi / Q000201:enzymology*
D001688:Biological Products; D005419:Flavonoids; D009097:Multienzyme Complexes; D015800:Protozoan Proteins; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases