Antimalarial and antioxidant activities of novel artesunate-ellagic acid hybrid compound in vitro and in vivo.

Introduction: Emergence of drug resistant strains of Plasmodium species has necessitated the search for novel antimalarials with unique mechanisms of action. Synthesis of hybrid compounds has been one approach to tackling this challenge. In this study, the synthesis of artesunate-ellagic acid hybrid compound (EA31) from ellagic acid and artesunate and its evaluation for antimalarial and antioxidant activities using in vitro and in vivo models were carried out. Method: EA31 was synthesized from artesunate and ellagic acid. The activities of the hybrid compound against Plasmodium falciparum W2 and P. berghei NK65 were evaluated, and its antioxidant activities were also determined. Results: The results revealed that EA31 was more active against P. falciparum W2 (chloroquine resistant) clone and less cytotoxic to buffalo green monkey kidney cell line compared to artesunate. EA31 was also active against Plasmodium berghei NK65 in vivo. The results revealed inhibition of ß-hematin formation as one of the mechanisms of action of EA31. EA31 also exhibited antioxidant activities. Conclusion: The results revealed that EA31 may exert dual action of killing malaria parasite and mopping the reactive oxygen species that mediate the secondary complications of malaria.

Light effects on Lasiodiplodia theobromae metabolome cultured in vitro.

INTRODUCTION: The present work identified and compared intracellular metabolites and metabolic networks in mycelial cultures of Lasiodiplodia theobromae grown under 12 natural light and 24 hours' dark using a 1 H NMR-based metabolomics approach. MATERIALS AND METHODS: Fungal cultures were grown in potato dextrose media, and metabolites were extracted by sonication with sodium phosphate-buffered saline (pH = 6.0, 10% D2O, 0.1 mM TSP) from mycelium samples collected every week over four weeks. RESULTS: Multivariate analyses revealed that the light exposure group showed a positive correlation within beta-hydroxybutyrate, acetoacetate, acetone, betaine, choline, glycerol, and phosphocholine. On the other hand, phenyl acetate, leucine, isoleucine, valine, and tyrosine were positively correlated with dark conditions. Light favored the oxidative degradation of valine, leucine, and isoleucine, leading to the accumulation of choline, phosphocholine, betaine, and ketone bodies (ketogenesis). Ketogenesis, gluconeogenesis, and the biosynthesis of choline, phosphocholine, and betaine, were considered discriminatory routes for light conditions. The light-sensing pathways were interlinked with fungal development, as verified by the increased production of mycelia biomass without fruiting bodies and stress signaling, as demonstrated by the increased production of pigments.

NMR investigation into the dynamic behaviour of a novel C2-symmetric macrocyclic ligand.

The variable-temperature (1)H NMR spectra of a tosylated triazacyclononane are reported. The spectra show a dynamic process which is assigned to hindered rotation about the amide-like N--S bonds, and a value for the free energy of activation for the rotations is derived, DeltaG* = 50.2 kJ mol(-1) at 273 K. Steric and electronic factors which influence the barrier are discussed.

Structure, modelling and dynamic behaviour of aza- and azaoxamacrocyclic ligands derived from (R,R)-1,2-diaminocyclohexane.

Investigations into the conformational behaviour of macrocyclic ligands 5 and 6 derived from (R,R)-1,2-diaminocyclohexane have been undertaken using molecular modelling, single crystal X-ray diffraction and variable temperature 1H NMR spectroscopy. These have revealed that the lowest energy conformers in both cases do not possess the expected C2-element of symmetry, which can only be accessed at higher temperatures. Instead both molecules exist as C1-conformers at room temperature and in the solid state. In solution a range of dynamic exchange processes is observed which result, in part from the inherent strain in these fused bicyclic systems. An unexpected but characteristic feature of the C1-symmetric conformers is highlighted by the presence of a signal at unexpectedly low field in their 1H NMR spectra due to the interaction of two of the sulfonyl oxygen atoms with one of the bridgehead hydrogen atoms.