Peptide derivatives and therapeutic activity thereof

Disclosed 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

A carnosine analog mitigates metabolic disorders of obesity by reducing carbonyl stress

Sugar- and lipid-derived aldehydes are reactive carbonyl species (RCS) frequently used as surrogate markers of oxidative stress in obesity. A pathogenic role for RCS in metabolic diseases of obesity remains controversial, however, partly because of their highly diffuse and broad reactivity and the lack of specific RCS-scavenging therapies. Naturally occurring histidine dipeptides (e.g., anserine and carnosine) show RCS reactivity, but their therapeutic potential in humans is limited by serum carnosinases. Here, we present the rational design, characterization, and pharmacological evaluation of carnosinol, i.e., (2S)-2-(3-amino propanoylamino)-3-(1H-imidazol-5-yl)propanol, a derivative of carnosine with high oral bioavailability that is resistant to carnosinases. Carnosinol displayed a suitable ADMET (absorption, distribution, metabolism, excretion, and toxicity) profile and was determined to have the greatest potency and selectivity toward \u3b1,\u3b2-unsaturated aldehydes (e.g., 4-hydroxynonenal, HNE, ACR) among all others reported thus far. In rodent models of diet-induced obesity and metabolic syndrome, carnosinol dose-dependently attenuated HNE adduct formation in liver and skeletal muscle, while simultaneously mitigating inflammation, dyslipidemia, insulin resistance, and steatohepatitis. These improvements in metabolic parameters with carnosinol were not due to changes in energy expenditure, physical activity, adiposity, or body weight. Collectively, our findings illustrate a pathogenic role for RCS in obesity-related metabolic disorders and provide validation for a promising new class of carbonyl-scavenging therapeutic compounds rationally derived from carnosine

Compositions containing d-carnosine

Disclosed are compositions containing D-carnosine as active ingredient, mixed with suitable vehicles or excipients

A NEW FLEXIBLE SYNTHESIS OF (R,S)-MEVALONOLACTONE

By 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)

PHARMACEUTICAL FORMULATIONS COMPRISING ACTIVE PHARMACEUTICAL PRINCIPLES ABSORBED ON TITANIUM DIOXIDE NANOPARTICLES.

The 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

AMINO ALCOHOL DERIVATIVES AND THEIR THERAPEUTIC ACTIVITIES

The 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 compound

AMINO ALCOHOL DERIVATIVES AND THEIR THERAPEUTIC ACTIVITIES.

The 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

AMINO ALCOHOL DERIVATIVES AND THEIR THERAPEUTIC ACTIVITIES.

The 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