A new synthesis of isoaurones: cytotoxic activity of compounds related to the alleged structure of isoaurostatin

A new synthesis of isoaurones related to the alleged structure of isoaurostatin, via Heck intramolecular cyclization of cinnamic esters of 2-iodophenols, is reported. The cytotoxic activity of these isoaurones is lower than that of the structurally very similar 4-arylcoumarins.     

Recombinant protein-co-PEG networks as cell-adhesive and proteolytically degradable hydrogel matrixes. Part I: Development and physicochemical characteristics

Toward the development of synthetic bioactive materials to support tissue repair, we present here the design, production, and characterization of genetically engineered protein polymers carrying specific key features of the natural extracellular matrix, as well as cross-linking with functionalized poly(ethylene glycol) (PEG) to form hybrid hydrogel networks. The repeating units of target recombinant protein polymers contain a cell-binding site for ligation of cell-surface integrin receptors and substrates for plasmin and matrix metalloproteinases (MMPs), proteases implicated in wound healing and tissue regeneration. Hydrogels were formed under physiological conditions via Michael-type conjugate addition of vinyl sulfone groups of end-functionalized PEG with thiols of cysteine residues, representing designed chemical cross-linking sites within recombinant proteins. Cross-linking kinetics was shown to increase with the pH of precursor solutions. The elastic moduli (G') and swelling ratios (Q(m)) of the resulting hydrogels could be varied as a function of the stoichiometry of the reacting groups and precursor concentration. Optima of G' and Q(m), maximum and minimum, respectively, were obtained at stoichiometry ratios r slightly in excess of 1 (r = cysteine/vinyl sulfone). The pool of technologies utilized here represents a promising approach for the development of artificial matrixes tailored for specific medical applications.     

The approximability of the String Barcoding problem

The String Barcoding (SBC) problem, introduced by Rash and Gusfield (RECOMB, 2002), consists in finding a minimum set of substrings that can be used to distinguish between all members of a set of given strings. In a computational biology context, the given strings represent a set of known viruses, while the substrings can be used as probes for an hybridization experiment via microarray. Eventually, one aims at the classification of new strings (unknown viruses) through the result of the hybridization experiment. In this paper we show that SBC is as hard to approximate as Set Cover. Furthermore, we show that the constrained version of SBC (with probes of bounded length) is also hard to approximate. These negative results are tight.     

Functionalized pyrazoles and pyrazolo[3,4-d]pyridazinones: Synthesis and evaluation of their phosphodiesterase 4 inhibitory activity

A series of pyrazoles and pyrazolo[3,4-d]pyridazinones were synthesized and evaluated for their PDE4 inhibitory activity. All the pyrazoles were found devoid of activity, whereas some of the novel pyrazolo[3,4-d]pyridazinones showed good activity as PDE4 inhibitors. The most potent compounds in this series showed an IC₅₀ in the nanomolar range. The ability to inhibit TNF-α release in human PBMCs was determined for two representative compounds, finding values in the sub-micromolar range. SARs studies demonstrated that the best arranged groups around the heterocyclic core are 2-chloro-, 2-methyl- and 3-nitrophenyl at position 2, an ethyl ester at position 4 and a small alkyl group at position 6. Molecular modeling studies performed on a representative compound allowed to define its binding mode to the PDE4B isoform.     

Combined effect of DHA and alpha-tocopherol enrichment on sperm quality and fertility in the turkey

The aim of the present study was to characterize the dietary effects of n-3 LC-PUFA and alpha-tocopheryl acetate (vE) on the quality, phospholipid fatty acid composition, alpha-tocopherol content (alpha-T) and in vitro susceptibility to lipid peroxidation in turkey semen. Fertility of fresh semen was also evaluated. Male turkeys were randomly divided and fed either a control diet or a fish oil and vE rich diet (FO diet) from 40 to 60 weeks of age. The FO diet increased the proportion of n-3 fatty acids in spermatozoa and as a consequence the (n-3)/(n-6) ratio also increased. These changes did not affect the proportion of n-9 PUFAs, particularly of C22:3n-9, in semen. The sperm content of alpha-T was dependent by the dietary supplementation of the vitamin and the sperm content was more than doubled supplying 120 mg kg(-1) of feed to the males compared to the 60 mg kg(-1) of feed in the control diet. In agreement with the major content of alpha-T in spermatozoa collected from the FO group were significantly less susceptible to in vitro induced oxidation. The reproductive capacity of the male breeders was not affected by the diet; however the result is considered of some relevance for field conditions where even very small changes have economic interest being applied to large bird population.     

The enantiomers of epiboxidine and of two related analogs: synthesis and estimation of their binding affinity at α4β2 and α7 neuronal nicotinic acetylcholine receptors

Epiboxidine hydrochlorides (+)-2 and (-)-2, which are the structural analogs of the antipodes of epibatidine (±)-1, as well as the enantiomeric pairs (+)-3/(-)-3 and (+)-4/(-)-4 were synthesized and tested for binding affinity at α4β2 and α7 nicotinic acetylcholine receptor (nAChR) subtypes. Final derivatives were prepared through the condensation of racemic N-Boc-7-azabicyclo[2.2.1]heptane-2-one (±)-5 with the resolving agent (R)-(+)-2-methyl-2-propanesulfinamide. The pharmacological analysis carried out on the three new enantiomeric pairs evidenced an overall negligible degree of enantioselectivity at both nAChRs subtypes, a result similar to that reported for both natural and unnatural epibatidine enantiomers at the same investigated receptor subtypes.