New Leishmania donovani nucleoside hydrolase inhibitors from Brazilian flora.

This study presents new inhibitors of the nucleoside hydrolase from Leishmania donovani (LdNH) with in vitro leishmanicidal activity. Biological screening of 214 Brazilian plant extracts was performed to select plants with enzyme inhibitory activity. Two plants were selected for their results, and for their lack of prior phytochemical description: Leandra amplexicaulis DC. (Melastomataceae) and Urvillea rufescens Cambess (Sapindaceae). Three flavonoids were isolated by bioguided fractionation of the hydroethanolic extracts: kaempferol 3-O-α-l-rhamnopyranoside (1) and kaempferol 3-O-ß-d-xylopyranosyl-(1→2)-α-l-rhamnopyranoside (2) from L. amplexicaulis, as well as tricetin-4'-O-methyl flavone (3) from U. rufescens. These flavonoids showed inhibitory activities (IC50) of 197.4 µM (1), 74.7 µM (2) and 1.1 µM (3) on the LdNH. Their binding mode was proposed based on molecular docking with LdNH and by NMR Saturation Transfer Difference studies. Kinetic studies demonstrate that the most potent inhibitor (3) acts by uncompetitive inhibition. This study reports for the first time the inhibition of LdNH by naturally sourced flavonoids.

Pseudallicins A-D: Four Complex Ovalicin Derivatives from Pseudallescheria boydii SNB-CN85.

The isolation and complete structural elucidation of four complex ovalicin analogues, named pseudallicins A-D, from the fungus Pseudallescheria boydii strain SNB-CN85 are described. On the basis of structural similarities and information from the literature, a joint biosynthetic pathway for the pseudallicins is proposed.

Aedes aegypti Larvicidal Sesquiterpene Alkaloids from Maytenus oblongata.

Four new sesquiterpene alkaloids (1-4) with a ß-dihydroagrofuran skeleton and a new triterpenoid (5) were isolated from an ethyl acetate extract of Maytenus oblongata stems. Their structures were elucidated using 1D and 2D NMR spectroscopy as well as MS and ECD experiments. The M. oblongata stem EtOAc extract and the pure compounds isolated were tested for larvicidal activity against Aedes aegypti under laboratory conditions, and compounds 2 and 3 were found to be active.

Reactivation of antibiosis in the entomogenous fungus Chrysoporthe sp. SNB-CN74.

Chrysoporthe sp. SNB-CN74 was isolated from a Nasutitermes corniger nest, and its ethyl acetate extract was found to exhibit very strong antibacterial activity. Two antibacterial metabolites were isolated, (-)-R-skyrin (2) and (+)-rugulosin A (3). Eventually, the fungus lost its antibiotic potential when subcultured, and the use of yeast extract induced the re-expression of these two antibiotics. Yeast extract possibly activated a cryptic pathway by mimicking the presence of an ecological competitor.

Antibacterial ilicicolinic acids C and D and ilicicolinal from Neonectria discophora SNB-CN63 isolated from a termite nest.

Ilicicolinic acids A, C, and D (1-3) and ilicicolinal (4) were isolated from a fungus isolated from a Nasutitermes corniger nest in French Guiana. The structures of ilicicolinic acids C and D and ilicicolinal were elucidated using 1D and 2D NMR spectroscopic data as well as MS data. Ilicicolinic acids show antibacterial activity in vitro.

Antifungal agents from Pseudallescheria boydii SNB-CN73 isolated from a Nasutitermes sp. termite.

Defense mutualisms between social insects and microorganisms have been described in the literature. The present article describes the discovery of a Pseudallescheria boydii strain isolated from Nasutitermes sp. The microbial symbiont produces two antifungal metabolites: tyroscherin and N-methyltyroscherin, a compound not previously described in the literature. Methylation of tyroscherin has confirmed the structure of N-methyltyroscherin. Both compounds are effective antifungal agents with favorable selectivity indices for Candida albicans and Trichophyton rubrum.

Larvicidal activity of isoflavonoids from Muellera frutescens extracts against Aedes aegypti.

The biological activity of extracts from the leaves, bark and roots of Muellera frutescens, an Amazonian ichtyotoxic plant, were evaluated to find new environmentally safe insecticides. The n-hexane extracts of bark, leaf, and root showed a strong toxic activity against Aedes aegypti mosquito larvae. Bioguided fractionation of the bark extract led to the isolation of seven isoflavonoids (12a-hydroxyelliptone, elliptone, (-)-variabilin, rotenone, rotenolone, tephrosin and deguelin). Rotenone and deguelin are responsible for the larvicidal activity of the plant. M frutescens leaves contain up to 0.6%, w/w, deguelin. These results justify the traditional ichtyotoxic use of M frutescens. The leaves contain a relatively high proportion of deguelin and, therefore, can be considered as a renewable source of this environmentally friendly insecticidal isoflavonoid.