| Autor: |
Casanova LM; Instituto de Pesquisas de Produtos Naturais, Centro de Ciências da Sau'de, Cidade Universita'ria , Universidade Federal do Rio de Janeiro , 21941-902 Rio de Janeiro , RJ , Brazil., Rodrigues LM; Instituto de Pesquisas de Produtos Naturais, Centro de Ciências da Sau'de, Cidade Universita'ria , Universidade Federal do Rio de Janeiro , 21941-902 Rio de Janeiro , RJ , Brazil., de Aguiar PF; Departamento de Química Analítica, Instituto de Química, Centro de Ciências Matemáticas e da Natureza, Cidade Universitária , Universidade Federal do Rio de Janeiro , 21941-909 Rio de Janeiro , RJ , Brazil., Tinoco LW; Instituto de Pesquisas de Produtos Naturais, Centro de Ciências da Sau'de, Cidade Universita'ria , Universidade Federal do Rio de Janeiro , 21941-902 Rio de Janeiro , RJ , Brazil. |
| Abstrakt: |
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 ( Ld NH) 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 Ld NH 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 Ld NH 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 Ld NH (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. |
