An NMR-Based Chemometric Strategy to Identify Leishmania donovani Nucleoside Hydrolase Inhibitors from the Brazilian Tree Ormosia arborea

Abstract

Nucleoside hydrolases are a strategic target for the development of drugs to treat leishmaniasis, a neglected disease that affects 700 thousand to one million people annually. The present study aimed to identify Leishmania donovani nucleoside hydrolase (LdNH) inhibitors from the leaves of Ormosia arborea, a tree endemic to Brazilian ecosystems, through a strategy based on 1 H NMR analyses and chemometrics. The aqueous EtOH extract of O. arborea leaves inhibited LdNH activity by 95%. The extract was fractionated in triplicate (13 in each step, making a total of 39 fractions). Partial least squares discriminant analysis (PLS-DA) was used to correlate the 1 H NMR spectra of the fractions with their LdNH inhibitory activity and thus to identify the spectral regions associated with the bioactivity. The strategy aimed at isolating the probable bioactive substances and led to two new A-type proanthocyanidins, linked to a p-coumaroyl unit (1 and 2), which appeared as noncompetitive inhibitors of LdNH (IC 50 : 28.2 ± 3.0 μM and 25.6 ± 4.1 μM, respectively). This study confirms the usefulness of the NMR-based chemometric methods to accelerate the discovery of drugs from natural products.

Metabolomic Analysis of Combretum lanceolatum Plants Interaction with Diaporthe phaseolorum and Trichoderma spirale Endophytic Fungi through 1H‐NMR

“…Two multivariate tools were used to analyse the metabolomic profiles of the plant extracts. Principal Component Analysis (PCA) was used to provide an overview of sample grouping and Partial Least Squares‐Discriminant Analysis (PLS‐DA) to provide a result of the discriminated by classes between treated plants and control [31] . Among the PCA and PLS‐DA analyses, the results suggest that over the interaction time between the plant and fungus the variation in metabolism becomes more significant.…”

“…Principal Component Analysis (PCA) was used to provide an overview of sample grouping and Partial Least Squares-Discriminant Analysis (PLS-DA) to provide a result of the discriminated by classes between treated plants and control. [31] Among the PCA and PLS-DA analyses, the results suggest that over the interaction time between the plant and fungus the variation in metabolism becomes more significant. The PCA score plot (Figure 3 -Chart A) and PLS-DA score plot (Figure 3 -Charts B) illustrate that the plant -Dp interaction have a distinct profile compared to the plant control.…”

Metabolomics Analysis of C. lanceolatum Roots in the Presence of Its Endophytic Fungi

“…The principal component analysis (PCA) was used to analyze the NMR data set and loading plots were used to detect the spectral areas (metabolites) responsible for separation in the data. 35 Data set obtained from the analysis of plant-Ts fungi interaction after 7 days of inoculation, the first two components model could explain 74.9%. Among the PCs, combination of PC1 and PC2 can give well-separated two clusters for plant-Ts fungi interaction as compared to the control plants (Figure 2a).…”

Identification of chemosensitizing agents of colorectal cancer in Rauvolfia vomitoria using an NMR-based chemometric approach

“…In this research, samples were considered as active if they were able to increase the anticancer activity of 5-FU by 50%. The OPLS-DA, well suited for the classification of many types of biological data that have multi-collinear and noisy variables, was performed to correlate the 1 H NMR spectra and chemosensitization effects of each fraction (Bylesjo et al, 2006;Casanova et al, 2020). Multivariate analysis of the NMR data of the 18 fractions from RVA and their proliferation inhibitory activity against two CRC cells were shown in Figure 5A.…”