Orthogonally Protected Diaminocyclopentenones as Synthons: Total Synthesis of (±)-Agelastatin A.

Natural products containing aminocyclopentanes are common secondary metabolites, often biologically active. This work aims at the preparation of a useful synthon for total synthesis containing orthogonally protected amines. To this end, furfural and two amines were employed to form mixed trans-4,5-diaminocyclopentenones promoted by Cu(OTf)2. The selected amines can be orthogonally deprotected, allowing selective modification of the amines on the cyclopentane core. Their utility was showcased for the total synthesis of highly complex (±)-Agelastatin A.

Taxonomic distribution, structure/function relationship and metabolic context of the two families of sulfide dehydrogenases: SQR and FCSD.

Hydrogen sulfide (H2S) is a versatile molecule with different functions in living organisms: it can work as a metabolite of sulfur and energetic metabolism or as a signaling molecule in higher Eukaryotes. H2S is also highly toxic since it is able to inhibit heme cooper oxygen reductases, preventing oxidative phosphorylation. Due to the fact that it can both inhibit and feed the respiratory chain, the immediate role of H2S on energy metabolism crucially relies on its bioavailability, meaning that studying the central players involved in the H2S homeostasis is key for understanding sulfide metabolism. Two different enzymes with sulfide oxidation activity (sulfide dehydrogenases) are known: flavocytochrome c sulfide dehydrogenase (FCSD), a sulfide:cytochrome c oxidoreductase; and sulfide:quinone oxidoreductase (SQR). In this work we performed a thorough bioinformatic study of SQRs and FCSDs and integrated all published data. We systematized several properties of these proteins: (i) nature of flavin binding, (ii) capping loops and (iii) presence of key amino acid residues. We also propose an update to the SQR classification system and discuss the role of these proteins in sulfur metabolism.

Polysaccharides isolated from Digenea simplex inhibit inflammatory and nociceptive responses.

Polysaccharides (PLS) have notably diverse pharmacological properties. In the present study, we investigated the previously unexplored anti-inflammatory and antinociceptive activities of the PLS fraction isolated from the marine red alga Digenea simplex. We found that the PLS fraction reduced carrageenan-induced edema in a dose-dependent manner, and inhibited inflammation induced by dextran, histamine, serotonin, and bradykinin. The fraction also inhibited neutrophil migration into both mouse paw and peritoneal cavity. This effect was accompanied by decreases in IL1-ß and TNF-α levels in the peritoneal fluid. Pre-treatment of mice with PLS (60 mg/kg) significantly reduced acetic acid-induced abdominal writhing. This same dose of PLS also reduced total licking time in both phases of a formalin test, and increased latency in a hot plate test. Therefore, we conclude that PLS extracted from D. simplex possess anti-inflammatory and antinociceptive activities and can be useful as therapeutic agents against inflammatory diseases.