Effect of leaf-cutting ant nests on plant growth in an oligotrophic Amazon rain forest

This study examined whether high nutrient concentrations associated with leaf-cutting ant nests influence plant growth and plant water relations in Amazon rain forests. Three nests of Atta cephalotes were selected along with 31 Amaioua guianensis and Protium sp. trees that were grouped into trees near and distant (>10 m) from nests. A 15N leaf-labelling experiment confirmed that trees located near nests accessed nutrients from nests. Trees near nests exhibited higher relative growth rates (based on stem diameter increases) on average compared with trees further away; however this was significant for A. guianensis (near nest 0.224 y−1 and far from nest 0.036 y−1) but not so for Protium sp. (0.146 y−1 and 0.114 y−1 respectively). Water relations were similarly species-specific; for A. guianensis, near-nest individuals showed significantly higher sap flow rates (16 vs. 5 cm h−1), higher predawn/midday water potentials (−0.66 vs. −0.98 MPa) and lower foliar δ13C than trees further away indicating greater water uptake in proximity to the nests while the Protium sp. showed no significant difference except for carbon isotopes. This study thus shows that plant response to high nutrient concentrations in an oligotrophic ecosystem varies with species. Lower seedling abundance and species richness on nests as compared with further away suggests that while adult plants access subterranean nutrient pools, the nest surfaces themselves do not encourage plant establishment and growth.

Design and Synthesis of 4-N-Alkanoyl and 4-N-Alkyl Gemcitabine Analogues Suitable for Positron Emission Tomography

Gemcitabine is a highly potent chemotherapeutic nucleoside agent used in the treatment of several cancers and solid tumors. However, it is therapeutically limitated because of toxicity to normal cells and its rapid intracellular deamination by cytidine deaminase into the inactive uracil derivative. Modification at the 4-(N) position of gemcitabine's exocyclic amine to an -amide functionality is a well reported prodrug strategy which has been that confers a resistance to intracellular deamination while also altering pharmacokinetics of the parent drug. Coupling of gemcitabine to carboxylic acids with varying terminal moieties afforded the 4-N-alkanoylgemcitabines whereas reaction of 4-N-tosylgemcitabine with the corresponding alkyl amines gave the 4-N-alkylgemcitabines. The 4-N-alkanoyl and 4-N-alkyl gemcitabine analogues with a terminal hydroxyl group on the 4-N-alkanoyl or 4-N-alkyl chain were efficiently fluorinated either with diethylaminosulfur trifluoride or under conditions that are compatible with the synthetic protocols for 18F labeling, such as displacement of the corresponding mesylate with KF/Kryptofix 2.2.2. The 4-N-alkanoylgemcitabine analogues displayed potent cytostatic activities against murine and human tumor cell lines with 50% inhibitory concentration (IC50) values in the range of low nM, whereas cytotoxicity of the 4-N-alkylgemcitabine derivatives were in the low to modest µM range. The cytostatic activity of the 4-N-alkanoylgemcitabines was reduced by several orders of magnitude in the 2'-deoxycytidine kinase (dCK)-deficient CEM/dCK- cell line while the 4-N-alkylgemcitabines were only lowered by 2-5 times. None of the 4-N-modified gemcitabines were found to be substrates for cytosolic dCK, however all were found to inhibit DNA synthesis. As such, the 4-N-alkanoyl gemcitabine derivatives likely need to be converted to gemcitabine prior to achieving their significant cytostatic potential, whereas the 4-N-alkylgemcitabines reach their modest activity without "measurable" conversion to gemcitabine. Thus, the 4-N-alkylgemcitabines provide valuable insight on the metabolism of 4-N-modified gemcitabine prodrugs.