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

NATALIA P. ALZA; EVA-MARIA PFERSCHY-WENZIG; SABINE ORTMANN; NADINE KRETSCHMER; OLAF KUNERT; GERALD RECHBERGER ; BAUER, RUDOLF; ANA PAULA MURRAY

Chemistry and Biodiversity

WILEY-V C H VERLAG GMBH

Lugar: Zurich; Año: 2014 vol. 11 p. 311 - 322

1612-1872

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,16a,23-tetrahydroxyolean-12-en-28-oic acid 28-O-ß-D-xylopyranosyl-(1--2)-ß-D-apiofuranosyl-(1--3)-ß-D-xylopyranosyl-(1--3)-a-L-rhamnopyranosyl-(1--2)-a-L-arabinopyranosyl ester, 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)-a-L-rhamnopyranosyl-(1--2)-a-L-arabinopyranosyl ester 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)-a-L-rhamnopyranosyl-(1→2)-a-L-arabinopyranosyl ester, named grindeliosides A-C. Their structures were determined by the extensive use of one and two-dimensional NMR experiments along with mass spectrometry analysis and chemical evidence. The isolated compounds were evaluated for their inhibitory activity against LPS/IFN-gamma-induced NO production in RAW 264.7 macrophages and for their cytotoxic activity against the human leukemic cell line CCRF-CEM and MRC-5 lung fibroblasts. Hispidulin markedly reduced LPS/IFN-gamma-induced NO production (IC50 51.4 µM) while grindeliosides A-C were found to be cytotoxic, being grindelioside C the most active against both CCRF-CEM (IC50 4.2 ± 0.1 microM) and MRC-5 (IC50 4.5 ± 0.1 microM) cell lines.