Preparation and biological evaluation of some 1,2-O-isopropylidene-D-hexofuranose esters

The synthesis and biological evaluation of some new glycose esters bearing the 1,2-O-isopropylidene-d-hexofuranose functionality and belonging to the 3-O-acyl-d-allose and 6-O-acyl-d-glucose series are reported. When the results concerning cell growth inhibition are compared, it appears that the 6-O-acyl-d-glucose derivatives are more active than the 3-O-acyl-d-allose compounds. Within both 6-O-acyl-d-glucose and 3-O-acyl-d-allose derivatives, butyric esters displayed the highest inhibitory effects. Inhibition of cell growth is not associated with high induction levels of erythroid differentiation, despite the fact that pivaloates induce erythroid differentiation to an extent similar to that exhibited by previously reported molecules [Bioorg. Med. Chem. Lett.1999, 9, 3153-3158].     

Coral communities of the northwestern Gulf of Aden (Yemen): variation in framework building related to environmental factors and biotic conditions

Coral communities were investigated in the northwestern Gulf of Aden, Yemen, for their composition, structure, and bioconstruction potential. Although no true reef was encountered, high cover coral carpets were found where hard substrate was available. Seven different types of coral communities were differentiated, and both non-framework and framework coral communities were found. Monotypy or oligotypy seem to be consistent characteristics of framework-building coral communities in the study area. Apart from substrate availability, proximity to the upwelling area and exposure were found to be the most important environmental factors influencing coral communities structure, composition, and bioconstruction potential.     

Antioxidant activity of oligomeric acylphloroglucinols from Myrtus communis L

The use of myrtle (Myrtus communis L.) as a culinary spice and as a flavoring agent for alcoholic beverages is widespread in the Mediterranean area, and especially in Sardinia. Myrtle contains unique oligomeric non-prenylated acylphloroglucinols, whose antioxidant activity was investigated in various systems. Both semimyrtucommulone (1) and myrtucommulone A (2) showed powerful antioxidant properties, protecting linoleic acid against free radical attack in simple in vitro systems, inhibiting its autoxidation and its FeCl3- and EDTA-mediated oxidation. While both compounds lacked pro-oxidant activity, semimyrtucommulone was more powerful than myrtucommulone A, and was further evaluated in rat liver homogenates for activity against lipid peroxidation induced by ferric-nitrilotriacetate, and in cell cultures for cytotoxicity and the inhibition of TBH- or FeCl3-induced oxidation. The results of these studies established semimyrtucommulone as a novel dietary antioxidant lead.     

A molecular phylogeny of antarctic chironomidae and its implications for biogeographical history

The chironomid midges Belgica antarctica, Eretmoptera murphyi (subfamily Orthocladiinae) and Parochlus steinenii (subfamily Podonominae), are the only Diptera species currently found in Antarctica. The relationships between these species and a range of further taxa of Chironomidae were examined by sequencing domains 1 and 3–5 of 28S ribosomal RNA. The resulting molecular relationships between B. antarctica and E. murphyi, within Orthocladiinae, were highly supported by validation analyses, confirming their position within Chironomidae, as generated by classical taxonomy. Within Podonominae, P. steinenii from the Maritime Antarctic was more closely related to material from sub-Antarctic South Georgia than to material from Patagonia. Taking advantage of the availability of a molecular substitution rate calculated for this gene in Diptera, a dating of divergence between our study taxa was tentatively established. The divergence dates obtained were 49 million years (Myr), between B. antarctica and E. murphyi, and 68.5 Myr between these species and the closest Orthocladiinae taxon tested from Patagonia, suggesting that B. antarctica and E. murphyi were representatives of an ancient lineage. As both are endemic to their respective tectonic microplates, their contemporary distribution is, therefore, likely to have been shaped by vicariance rather than dispersal.     

Chroman and tetrahydroquinoline ureas as potent TRPV1 antagonists

Novel chroman and tetrahydroquinoline ureas were synthesized and evaluated for their activity as TRPV1 antagonists. It was found that aryl substituents on the 7- or 8-position of both bicyclic scaffolds imparted the best in vitro potency at TRPV1. The most potent chroman ureas were assessed in chronic and acute pain models, and compounds with the ability to cross the blood-brain barrier were shown to be highly efficacious. The tetrahydroquinoline ureas were found to be potent CYP3A4 inhibitors, but replacement of bulky substituents at the nitrogen atom of the tetrahydroisoquinoline moiety with small groups such as methyl can minimize the inhibition.     

Ionic Currents of Human Trabecular Meshwork Cells from Control and Glaucoma Subjects

Increasing evidence suggests that trabecular meshwork (TM) cells participate in the regulation of intraocular pressure by controlling the rate of filtration of the aqueous humor. Ionic conductances that regulate cell volume and shape have been suggested to play an important role in TM cell volume regulation. Here, we compared ionic currents from TM cells derived from a normal subject (CTM) and from an individual affected by glaucoma (GTM). We found that while the ionic current types were similar, the current amplitudes and percentage of cells endowed with specific current at baseline were different in the two cell lines. Thus, we found that the majority of CTM cells were endowed with a swelling-activated Cl^? current at baseline, whereas in the majority of GTM cells this current was not active at baseline and became activated only after perfusion with a hypotonic solution. An inward rectifier K⁺ current was also more prevalent in CTM than in GTM cells. Our work suggests that disregulation of one or more of these ionic currents may be at the basis of TM cell participation in the development of glaucoma.