No abstract

Development of a 99mTc-labelled glucose derivative as a single-photon emission computed tomography analogue to [ 18 F]-2-fluoro-2-deoxy-D-glucose (FDG) is considered of great interest. Herein, we present the synthesis and preliminary bioevaluation of a 99m Tc(CO) 3 -glucose derivative. Derivatization of glucose at C2 was achieved using the so-called 'click chemistry', forming a histidine-like, 1,4-disubstituted triazole adequate as donor atom system for Tc(I)-tricarbonyl complexes. Synthesis of the intermediate azide derivative was achieved by conventional organic chemistry. Because of the efficiency and selectivity of this cycloaddition, labelling was performed in 'one pot', adding the tricarbonyl precursor fac-[ 99m Tc(CO) 3 (H 2 O) 3 ] + to the same vial where the click reaction has taken place without any further purification. A single product with radiochemical purity higher than 90% was obtained. It was stable for at least 4 h in reaction milieu and exhibited high hidrophilicity (log P of À1.2) and low binding to plasma proteins (5 AE 1%). Biodistribution in C57BL/6 mice bearing induced Lewis murine lung carcinoma is characterized by low blood and liver uptake and rapid urinary excretion. 99m Tc complex showed moderate tumour uptake but significant retention until 2 h post-injection. Soft tissue clearance was fast leading to significantly higher uptake in tumour in comparison to muscle (p = 0.05) at all time points. Overall, biodistribution of our compound was very similar to that of [ 18 F]-FDG. However, tumour uptake was significantly higher for [ 18 F]-FDG, probably because of high hidrophilicity of our derivative that may hinder cell penetration. Similarity to biodistribution of FDG is a promising outcome, and modifications of the chelator and linker might improve biological results.

No abstract

No abstract

The synthesis of cyclotetrapeptides analogues of the natural products tentoxin and versicotide D was achieved in good yield by solid phase peptide synthesis (SPPS) of their linear precursors and solution phase cyclization. All the cyclopeptides and several open precursors were evaluated as herbicides. Five cyclopeptides and five lineal peptides showed a significant inhibition (>70%) of Ryegrass seed’s radicle growth at 67 μg/mL. The evaluation at lower concentrations (4–11 μM) indicates two cyclopeptides analogs of tentoxin, which present one (N-Methyl-d-Phe), and two N-MeAA (N-Methyl-Ala and N-Methyl-Phe), respectively, as the most active of them, showing remarkable phytotoxic activity. In two cases, the open precursors are as active as their corresponding cyclopeptide. However, many linear peptides are inactive and their cyclization derivatives showed herbicidal activity. In addition, two cyclopeptide analogues of versicotide D showed more improved activity than the natural product. The results indicate that the peptide sequence, the amino acid stereochemistry and the presence of N-methyl group have important influence on the phytotoxic activity. Moreover, several compounds could be considered as lead candidates in the development of bioherbicides.

No abstract

Macrocycles possess desirable properties that make them promising candidates for the discovery of novel drugs. They present structural features to favor bioactive conformations, selectivity to the receptors, cell permeability and metabolic stability. More effective and nontoxic drugs to cure human African trypanosomiasis, Leishmaniasis and Chagas disease are needed, especially because resistance has been detected. Therefore, major efforts should be made for investigation in new bioactive compounds exhibiting different mechanisms of action. Macrocycles might fulfill the expectations for the development of new drugs to treat those diseases. In the current review, we focus on macrocycles exhibiting biological activities as antitrypanosomal and/or antileishmanial. The isolation, synthetic and biological studies of this class of compounds published from 2005 to 2014 are summarized.

Macrocycle analogs and key fragments of aerucyclamides were obtained and evaluated against Trypanosoma brucei brucei.