Withanolide Profile and Acetylcholinesterase Inhibitory Activity of Two Argentinean Jaborosa Species.

Acetylcholinesterase (AChE) inhibitors are still an important option for managing symptoms of mild to moderate Alzheimer's disease. In this study, we aimed to evaluate the potential in vitro AChE inhibitory activity of two Argentinian endemic Solanaceae species, Jaborosa bergii and J. runcinata. UHPLC-DAD-HRMS metabolite profiling revealed the presence of withanolides in the active CH2Cl2 subextracts. Their fractionation led to the isolation and identification of two known spiranoid withanolides from J. runcinata and three new withanolides with a skeleton similar to that of trechonolide-type withanolides from J. bergii. The known compounds showed moderate AChE inhibitory activity, while the new ones were inactive.

In Vitro Antileishmanial Activity of Sterols from Trametes versicolor (Bres. Rivarden).

Two ergostanes, 5α,8α-epidioxy-22E-ergosta-6,22-dien-3ß-ol (1) and 5α-ergost-7,22-dien-3ß-ol (2), and a lanostane, 3ß-hydroxylanostan-8,24-diene-21-oic acid (trametenolic acid) (3), were isolated from an n-hexane extract prepared from the fruiting body of Trametes versicolor (Bres. Rivarden). The activity of the isolated sterols was evaluated against promastigotes and amastigotes of Leishmania amazonensis Lainson and Shaw, 1972. The lanostane, compound (3), showed the best inhibitory response (IC50 promastigotes 2.9 ± 0.1 µM and IC50 amastigotes 1.6 ± 0.1 µM). This effect was 25-fold higher compared with its cytotoxic effect on peritoneal macrophages from BALB/c mice. Therefore, trametenolic acid could be regarded as a promising lead for the synthesis of compounds with antileishmanial activity.

Inhibition of NO production by Grindelia argentina and isolation of three new cytotoxic saponins.

A bioassay-guided phytochemical analysis of the ethanolic extract of Grindelia argentina Deble & Oliveira-Deble (Asteraceae) allowed the isolation of a known flavone, hispidulin, and three new oleanane-type saponins, 3-O-ß-D-xylopyranosyl-(1→3)-ß-D-glucopyranosyl-2ß,3ß,16α,23-tetrahydroxyolean-12-en-28-oic acid 28-O-ß-D-xylopyranosyl-(1→2)-ß-D-apiofuranosyl-(1→3)-ß-D-xylopyranosyl-(1→3)-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl ester (2), 3-O-ß-D-glucopyranosyl-2ß,3ß,23-trihydroxyolean-12-en-28-oic acid 28-O-ß-D-xylopyranosyl-(1→2)-ß-D-apiofuranosyl-(1→3)-ß-D-xylopyranosyl-(1→3)-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl ester, (3) and 3-O-ß-D-xylopyranosyl-(1→3)-ß-D-glucopyranosyl-2ß,3ß,23-trihydroxyolean-12-en-28-oic acid 28-O-ß-D-xylopyranosyl-(1→2)-ß-D-apiofuranosyl-(1→3)-ß-D-xylopyranosyl-(1→3)-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl ester (4), named grindeliosides A-C, respectively. Their structures were determined by extensive 1D- and 2D-NMR experiments along with mass spectrometry and chemical evidence. The isolated compounds were evaluated for their inhibitory activities against LPS/IFN-γ-induced NO production in RAW 264.7 macrophages and for their cytotoxic activities against the human leukemic cell line CCRF-CEM and MRC-5 lung fibroblasts. Hispidulin markedly reduced LPS/IFN-γ-induced NO production (IC50 51.4 µM), while grindeliosides A-C were found to be cytotoxic, with grindelioside C being the most active against both CCRF-CEM (IC50 4.2±0.1 µM) and MRC-5 (IC50 4.5±0.1 µM) cell lines.

Antiparasitic compounds from Cupania cinerea with activities against Plasmodium falciparum and Trypanosoma brucei rhodesiense.

In a survey of plants from Ecuador with antiprotozoal activity, Cupania cinerea was found to show significant in vitro activity against the Plasmodium falciparum K1 strain and Trypanosoma brucei rhodesiense. Subsequently, activity-guided isolation of the n-hexane and dichloromethane extracts from the bark of C. cinerea afforded two diterpene glycosides (1 and 2), named cupacinoside and 6'-de-O-acetylcupacinoside, and a lactonized triterpene bearing an oxepin moiety named cupacinoxepin (3), together with the known compounds scopoletin (4), caryophyllene oxide (5), two bisabolane sesquiterpenes (6 and 7), lichexanthone (8), gustastatin (9), lupenone (10), betulone (11), 17ß,21ß-epoxyhopan-3-one (12), taraxerol (13), and taraxerone (14). For compound 3, X-ray crystallography was employed to elucidate the relative configuration. For cupacinosides (1) and (2) and cupacinoxepin (3), in vitro activities against the P. falciparum K1 strain (IC(50)1, 1.3; 2, 1.8; and 3, 8.7 µM) and T. b. rhodesiense (IC(50)1, 4.5; 2, 15.8; and 3, 71.6 µM) were found. Cytotoxicity toward L-6 cells is discussed for all the compounds isolated.

Jacaranone-derived glucosidic esters from Jacaranda glabra and their activity against Plasmodium falciparum.

In a survey of plants from Ecuador with antiprotozoal activity, Jacaranda glabra was found to show promising activity against the Plasmodium falciparum K1 strain. Subsequently, activity-guided isolation of the dichloromethane extract from the leaves of J. glabra afforded four new phenylethanoid glucosides containing jacaranone-type moieties (1-4), named jacaglabrosides A-D. Their chemical structures were identified using NMR spectroscopy and MS techniques. The compounds were found to be active in vitro against the P. falciparum K1 strain (IC(50) 1, 1.02; 2, 0.56; 3, 0.56; and 4, 0.55 microg/mL) and generally possessed a low cytotoxicity toward L-6 cells, with the exception of compound 1 (IC(50) 1, 8.3; 2, >90; 3, 87; and 4, 85 microg/mL).