1,720,974 research outputs found
Compositions containing d-carnosine
No full textDisclosed are compositions containing D-carnosine as active ingredient, mixed with suitable vehicles or excipients
A NEW FLEXIBLE SYNTHESIS OF (R,S)-MEVALONOLACTONE
No full textBy selective ozonolysis of the diene (5), a new synthesis of (R,S)-mevalonolactone (1a) has been developed, which can be adapted to other compounds related to (1a). This has been exemplified by the synthesis of the monodeuteriated triol (4d) and dideuteriated mevalonolactone (1d)
The discovery of carnosine derivatives as selective and efficient sequestering agents of cytotoxic carbonyl species : from molecular design to preclinical studies
No full textObjective: Reactive carbonyl species (RCS) are involved in the pathogenesis of several human diseases. Hence RCS, apart from being considered a biomarker of oxidative damage, are also potential targets for the development of bioactive compounds acting as detoxifying agents of RCS (carbonyl quenching compounds). We found that the natural dipeptide carnosine (β-alanyl-L-histidine, L-CAR) is a selective and potent RCS sequestering agent, even though its clinical application is limited due to its rapid hydrolysis in blood by a specific dipeptidase (carnosinase). The enantiomer β-alanyl-D-histidine (D-CAR) showed a quenching activity nearly identical to that of L-CAR and was totally stable in the plasma. But while L-CAR is actively absorbed by hPepT1 transporter, D-CAR is scarcely transported. Consequently, we developed a drug discovery approach aimed at designing, synthesizing and evaluating novel CAR derivatives and peptidomimetics stable to carnosinase and bioavailable.
Methods: Two different approaches were considered, the first, aimed at increasing the oral bioavailability of D-CAR, by synthesizing a set of ester, amide and carbamate based prodrugs. The second approach was aimed at designing L-CAR peptidomimetic which are recognized by hPepT1 and hence transported through an active transport but not recognized by carnosinase.
Results: Among D-CAR prodrugs, the octyl ester of D-CAR was chosen as a candidate due to its favorable oral bioavailability (plasma D-CAR is increased 2.6-fold if given as an octyl ester relative to D-CAR). The octyl ester was then found to dose-dependently decrease the development of hypertension and dyslipidemia, to restore renal functions in Zucker fa/fa obese rats, and to inhibit the carbonylation process (AGEs and pentosidine). The compound coded FL-926-A16 was then selected among L-CAR peptidomimetics due to its following properties: ability to quench RCS, suitable bioavailability and resistance to carnosinase. The ability of FL-926-A16 to quench 4-hydroxy-trans-nonenal and to reduce protein carbonylation and tissue damage was then demonstrated in different animal models (db/db mouse and ApoE null mice).
Conclusion: Bioavailable CAR derivatives are promising bioactive molecules designed to reduce protein carbonylation through a sequestering mechanism of cytotoxic carbonyl species and were found greatly effective in different animal models of diabetic and non-diabetic nephropathy
AMINO ALCOHOL DERIVATIVES AND THEIR THERAPEUTIC ACTIVITIES.
No full textThe present invention relates to amino alcohol derivatives of general formula I: These derivatives possess an interesting activity in that they block the secondary products of lipid oxidative stress, and are consequently suitable for therapeutic use in all disorders related with the presence of reactive carbonyl compounds
Peptide derivatives and therapeutic activity thereof
Full text linkDisclosed are peptide or pseudopeptide derivatives containing a nitrogenous heterocyclic residue with blocking activity against the by-products of lipid oxidative, stress, and in particular of unsaturated aldehydes such as malondialdehyde and 4-hydroxy-trans-2-nonenal (HNE). Formula (I
Derivati di aminoalcoli e loro attività terapeutica
No full textThe present invention relates to amino alcohol derivatives of general formula I: These derivatives possess an interesting activity in that they block the secondary products of lipid oxidative stress, and are consequently suitable for therapeutic use in all disorders related with the presence of reactive carbonyl compounds
The discovery of carnosine derivatives as selective and efficient sequestering agents of cytotoxic carbonyl species : from molecular design to preclinical studies
No full text
Chemo-enzymatic approach to D-allo-isoleucine
No full textA mixture of D-alloisoleucine and L-isoleucine derivatives are selectively hydrolysed by enzymatic catalysis (alcalase) allowing the recovery of the D-allo stereoisomer in excellent d.e. and yields. Thus, N-formyl-D-allo-isoleucine benzylester is obtained after enzymatic hydrolysis of the diastereoisomeric mixture or by a crystallisation procedure. (C) 2003 Elsevier Ltd. All rights reserved
PHARMACEUTICAL FORMULATIONS COMPRISING ACTIVE PHARMACEUTICAL PRINCIPLES ABSORBED ON TITANIUM DIOXIDE NANOPARTICLES.
No full textThe invention provides methods for the adsorption of an active pharmaceutical ingredient on titianium dioxide nanoparticles which can be orally ingested allowing the drug release into the intestine without causing side effects to the upper gastrointestinal region
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