Insect antifeedant compounds from Nothofagus dombeyi and N. pumilio

A bioassay-guided purification of the extracts of Nothofagus dombeyi and N. pumilio leaves yielded several triterpenes and flavonoids including 2-O-acetylmaslinic acid, 3-O-acetyl 20,24,25-trihydroxydammarane, and 3,20,24,25-tetrahydroxydammarane as new natural products. All the isolated compounds were assessed for antifeeding activity against the 5th instar larvae of Ctenopsteustis obliquana. 12-Hydroxyoleanolic lactone and pectolinarigenin from N. dombeyi and dihydrooroxylin A from N. pumilio, showed significant antifeeding activity. © 2004 Elsevier Ltd. All rights reserved

Cytotoxic farnesyl glycosides from Pittosporum pancheri

International audienc

Pipestelides A–C: Cyclodepsipeptides from the Pacific Marine Sponge <i>Pipestela candelabra</i>

Pipestelides A–C (<b>2</b>–<b>4</b>) are three new NRPS–PKS hybrid macrolides containing uncommon moieties, isolated from the Pacific marine sponge <i>Pipestela candelabra</i>. Their structures were elucidated on the basis of spectroscopic data. These cyclodepsipeptides appear to be biosynthetically related to jaspamide (aka jasplakinolide) (<b>1</b>) by chemical modification of the building blocks of the polyketide or peptide chains. Pipestelides A–C (<b>2</b>–<b>4</b>) contain a bromotyrosine [3-amino-3-(bromo-4-hydroxyphenyl)­propanoic acid] unit, a polypropionate with a <i>Z</i> double bond, and a 2-hydroxyquinolinone, respectively. Revised chemical shift assignments are provided for the co-isolated known jasplakinolide C_a (<b>5</b>). In addition, compounds <b>2</b> and <b>3</b> exhibited cytotoxic activities in the micromolar range

mTOR inhibition via displacement of phosphatidic acid induces enhanced cytotoxicity specifically in cancer cells

International audienceThe mTOR is a central regulator of cell growth and is highly activated in cancer cells to allow rapid tumor growth. The use of mTOR inhibitors as anticancer therapy has been approved for some types of tumors, albeit with modest results. We recently reported the synthesis of ICSN3250, a halitulin analogue with enhanced cytotoxicity. We report here that ICSN3250 is a specific mTOR inhibitor that operates through a mechanism distinct from those described for previous mTOR inhibitors. ICSN3250 competed with and displaced phosphatidic acid from the FRB domain in mTOR, thus preventing mTOR activation and leading to cytotoxicity. Docking and molecular dynamics simulations evidenced not only the high conformational plasticity of the FRB domain, but also the specific interactions of both ICSN3250 and phosphatidic acid with the FRB domain in mTOR. Furthermore, ICSN3250 toxicity was shown to act specifically in cancer cells, as noncancer cells showed up to 100-fold less sensitivity to ICSN3250, in contrast to other mTOR inhibitors that did not show selectivity. Thus, our results define ICSN3250 as a new class of mTOR inhibitors that specifically targets cancer cells.Significance: ICSN3250 defines a new class of mTORC1 inhibitors that displaces phosphatidic acid at the FRB domain of mTOR, inducing cell death specifically in cancer cells but not in noncancer cells

Efficient Biostimulation of Native and Introduced Quorum-Quenching Rhodococcus erythropolis Populations Is Revealed by a Combination of Analytical Chemistry, Microbiology, and Pyrosequencing

Degradation of the quorum-sensing (QS) signals known as N-acylhomoserine lactones (AHL) by soil bacteria may be useful as a beneficial trait for protecting crops, such as potato plants, against the worldwide pathogen Pectobacterium. In this work, analytical chemistry and microbial and molecular approaches were combined to explore and compare biostimulation of native and introduced AHL-degrading Rhodococcus erythropolis populations in the rhizosphere of potato plants cultivated in farm greenhouses under hydroponic conditions. We first identified gamma-heptalactone (GHL) as a novel biostimulating agent that efficiently promotes plant root colonization by AHL-degrading R. erythropolis population. We also characterized an AHL-degrading biocontrol R. erythropolis isolate, R138, which was introduced in the potato rhizosphere. Moreover, root colonization by AHL-degrading bacteria receiving different combinations of GHL and R138 treatments was compared by using a cultivation-based approach (percentage of AHL-degrading bacteria), pyrosequencing of PCR-amplified rrs loci (total bacterial community), and quantitative PCR (qPCR) of the qsdA gene, which encodes an AHL lactonase in R. erythropolis. Higher densities of the AHL-degrading R. erythropolis population in the rhizosphere were observed when GHL treatment was associated with biocontrol strain R138. Under this condition, the introduced R. erythropolis population displaced the native R. erythropolis population. Finally, chemical analyses revealed that GHL, gamma-caprolactone (GCL), and their by-products, gamma-hydroxyheptanoic acid and gamma-hydroxycaproic acid, rapidly disappeared from the rhizosphere and did not accumulate in plant tissues. This integrative study highlights biostimulation as a potential innovative approach for improving root colonization by beneficial bacteria