Search

Sustainable agriculture requires balancing crop yields with the effects of pesticides on non-target organisms, such as bees and other crop pollinators. Field studies demonstrated that agricultural use of neonicotinoid insecticides can negatively affect wild bee species1,2, leading to restrictions on these compounds3. However, besides neonicotinoids, field-based evidence of the effects of landscape pesticide exposure on wild bees is lacking. Bees encounter many pesticides in agricultural landscapes4–9and the effects of this landscape exposure on colony growth and development of any bee species remains unknown. Here we show that the many pesticides found in bumble bee-collected pollen are associated with reduced colony performance during crop bloom, especially in simplified landscapes with intensive agricultural practices. Our results from 316 Bombus terrestriscolonies at 106 agricultural sites across eight European countries confirm that the regulatory system fails to sufficiently prevent pesticide-related impacts on non-target organisms, even for a eusocial pollinator species in which colony size may buffer against such impacts10,11. These findings support the need for postapproval monitoring of both pesticide exposure and effects to confirm that the regulatory process is sufficiently protective in limiting the collateral environmental damage of agricultural pesticide use.

The tumor microenvironment is characterized by a poor circulation which results in the selection of neoplastic cells that can grow or survive under hypoxic conditions. The relationship between hypoxia and histone deacetylase (HDAC) inhibitors has been previously established. In this work we evaluated the effects of novel HDAC inhibitors (the natural peptide FR235222 and three tetrapeptide analogs) in the human breast cancer cell line MDAMB231, cultured under hypoxia (2 O2 14 mmHg) or normoxia (20 O2 140 mmHg). First, we found that the novel HDAC inhibitors reduced cell proliferation in MDAMB231 cells at an extent which was similar or even higher than that exerted by the classic HDAC inhibitors trichostatin-A and suberoylanilide hydroxamic acid. More interestingly, the antiproliferative effects of the novel HDAC inhibitors were, in general, significantly higher in hypoxic cells than in normoxic controls. Hypoxic MDAMB231 cells expressed high levels of the hypoxia-inducible factor (HIF)-1 and HIF-1-related genes, such as vascular endothelial growth factor, Bcl-2/E1B 19 kDa interacting protein-3, glucose transporter-1, carbonic anhydrase IX, as determined by Western blot analysis and qRT-PCR. Finally, we found that HIF-1 and HIF-1-related genes were significantly downregulated by FR235222 and analogs. In conclusion, the identification of novel effects exerted by the HDAC inhibitors, characterized by a strong efficacy in inhibiting the expression of HIF-1 and its related genes, may have important implications in the pharmacological control of several tumors, including breast cancer, characterized by the presence of hypoxia, angiogenesis and metabolic derangements.

The introduction of a cyclic amino acid in a peptide is one of the best methods to rigidify a strand. A general approach towards a new class of seven‐membered ring amino acids is described starting from (S)‐tribenzyl glutamic acid γ‐aldehyde, which reacts with β‐keto phosphonates to generate the Horner–Wadsworth–Emmons product. In the presence of H2and a Pd catalyst, a four‐step process occurs involving double‐bond hydrogenation, hydrogenolysis of three benzyl protecting groups, imine formation, and reductive amination to produce the 7‐substituted azepane carboxylic acid in good overall yield and with good to excellent diastereomeric ratios. An amino function can be introduced in the 7‐position as an additional orthogonal chemical handle for readily generating diversity on the cyclic amino acid scaffold by using a β‐keto phosphonate derived from amino acids. A cyclic RGD (Arg‐Gly‐Asp) pentapeptide analogue containing this new class of noncoded amino acids was also prepared by microwave‐assisted cyclization, showing a promising activity as αvβ3integrin inhibitor.

Tamed by chelation: The MgBr2chelation of prochiral malonaldehydes allows diastereoselective monoaddition reactions with allyl stannane nucleophiles (see scheme; PG=protecting group, TBDMS=tert‐butyldiphenylmethylsilyl, Tr=trityl). In the same pot, addition of a second nucleophile proceeds in high diastereoselectivity to generate nonsymmetric products with up to five contiguous stereogenic centers, including a chiral all‐carbon quaternary center.

Durch Chelatisierung von MgBr2„gezähmte“prochirale Malonaldehyde gehen diastereoselektive Monoadditionen mit Allylstannanen ein (siehe Schema; PG=Schutzgruppe, TBDMS=tert‐Butyldiphenylmethylsilyl, Tr=Trityl). Durch die anschließende Addition eines zweiten Nucleophils in demselben Reaktionsgefäß gelangt man hoch diastereoselektiv zu unsymmetrischen Produkten mit bis zu fünf benachbarten Stereozentren (eines davon ein quartäres Kohlenstoffzentrum).

No Abstract

No Abstract

A convenient procedure is developed for domino hydroformylation cyclization reactions of unsaturated alcohols, amines and amides to produce various O‐ and N‐containing heterocycles.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.