Biological Activity of Novel Synthetic Derivatives of Carnosine

Stvolinsky, S. L.; Bulygina, E. R.; Федорова, Т. Н.; Meguro, Kanji; Sato, T.; Tyulina, O. V.; Abe, Hiroki; Boldyrev, Alexander A.

doi:10.1007/s10571-009-9462-7

Cited by 43 publications

(21 citation statements)

References 27 publications

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“…We also examined carnosine as a positive control. Previous studies have demonstrated carnosine is significant antioxidant and anti-ischemic propertied in the brain (Stvolinsky and Dobrota, 2000;Dobrota et al, 2005;Stvolinsky et al, 2010) and also able to protect human neuroblastoma SH-SY5Y cells against OGD. In this evaluation, protective effects of compounds 1-3 against ischemic-like OGD were 3.6, 2.9 and 2.3 times more effective than carnosine, respectively (Table II).…”

Section: Resultsmentioning

confidence: 99%

Inhibitory effect of 2-arylbenzofurans from the Mori Cortex Radicis (Moraceae) on oxygen glucose deprivation (OGD)-induced cell death of SH-SY5Y cells

et al. 2011

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Three known 2-arylbenzofurans, moracin P (1), moracin O (2) and mulberrofuran Q (3) were isolated from the MeOH extract of the Mori Cortex Radicis. These compounds 1-3 enhanced cell viability in dose-dependent manner against oxygen-glucose deprivation (OGD)-induced cell death in neuroblastoma SH-SY5Y cells, which was measured by MTT reduction assay. (EC(50) values of 10.4, 12.6, and 15.9 μM, respectively). In addition, the compounds 1-3 were examined for their inhibitory effect on OGD-induced ROS production by FACS analysis. We observed these compounds reduced ROS production in OGD-induced cell death (IC(50) values of 1.9, 0.3 and 12.1 μM, respectively). Consequently, reactive oxygen species (ROS) were overexpressed in OGD-induced cells and all three compounds reduced ROS induced by OGD in dosedependent manner. Taken together, compounds 1-3 might protect neuronal cell death against the oxidative stress induced by OGD, though further studies in vitro and in vivo models are necessary.

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Section: Resultsmentioning

confidence: 99%

Inhibitory effect of 2-arylbenzofurans from the Mori Cortex Radicis (Moraceae) on oxygen glucose deprivation (OGD)-induced cell death of SH-SY5Y cells

et al. 2011

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“…The analogs modified in the amino group also include cyclodextrin derivatives (Amorini et al 2007), glycoside analogs (Lanza et al 2011) and Trolox modified derivatives (Stvolinsky et al 2010). These compounds are stable in human plasma, but the large (and stable) modifications in the N-terminus prevent the carbonyl scavenging and indeed these compounds have been designed mainly as radical scavengers and/or metal chelators.…”

Section: Carnosine Derivatives: Improving Oral Bioavailability and DImentioning

confidence: 99%

Transforming dietary peptides in promising lead compounds: the case of bioavailable carnosine analogs

Vistoli

Carini

2012

Amino Acids

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The ability of carnosine to prevent advanced glycoxidation end products (AGEs) and advanced lipoxidation end products (ALEs) formation, on the one hand, and the convincing evidence that these compounds act as pathogenetic factors, on the other hand, strongly support carnosine as a promising therapeutic agent for oxidative-based diseases. The mechanism/s by which carnosine inhibits AGEs and ALEs is still under investigation but an emerging hypothesis is that carnosine acts by deactivating the AGEs and ALEs precursors and in particular the reactive carbonyl species (RCS) generated by both lipid and sugar oxidation. The ability of carnosine to inhibit AGEs and ALEs formation and the corresponding biological effects has been demonstrated in several in vitro studies and in some animal models. However, such effects are in line of principle, limited in humans, due to the effect of serum carnosinase (absent in rodents), which catalyzes the carnosine hydrolysis to its constitutive amino acids. Such a limitation has prompted a great interest in the design of carnosine derivatives, which maintaining (or improving) the reactivity with RCS, are more resistant to carnosinase. The present paper intends to critically review the most recent studies oriented to obtaining carnosine derivatives, optimized in terms of reactivity with RCS, selectivity (no reaction with physiological aldehydes) and the pharmacokinetic profile (mainly through an enhanced resistance to carnosinase hydrolysis). The review also includes a brief description of AGEs and ALEs as drug targets and the evidence so far reported regarding the ability of carnosine as inhibitor of AGEs and ALEs formation and the proposed reaction mechanisms.

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“…STC and RTC were concluded to demonstrate higher antioxidant capacity and better ability to prevent cerebellar neurons from ROS accumulation than their precursors, carnosine and trolox (Reviewed in Ref. [382]). Overall, natural low molecular mass antioxidant peptidomimetics add significantly to the defense provided by the enzymes superoxide dismutase, catalase and glutathione peroxidases [371,372].…”

Section: The Role Of Carnosine N-acetyl-carnosine and Carcinine Natumentioning

confidence: 99%

Structural and Functional Properties, Chaperone Activity and Posttranslational Modifications of Alpha-Crystallin and its Related Subunits in the Crystalline Lens: N-acetylcarnosine, Carnosine and Carcinine act as Alpha- Crystallin/Small Heat Shock Protein Enhancers in Prevention and Dissolution of Cataract in Ocular Drug Delivery Formulations of Novel Therapeutic Agents

Babizhayev¹

2012

DDF

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Cataract is a leading cause of blindness worldwide and is responsible for ∼40-80% of the estimated 45 million cases of blindness that occur across the globe. In addition to providing refractive properties to the lens for focusing the image, it is believed that the molecular chaperone function of α-crystallin is essential in preventing the light scattering due to aggregation of other proteins and thus in the maintenance of lens transparency and thereby prevention of cataract. By now, it is fairly acknowledged that chaperoning ability of α-crystallin is instrumental in the maintenance of crystalline lens transparency, and decreased chaperone-like activity of α-crystallin is associated with various types and stages of cataract. A better pharmacological targeting of safeguarding the α-crystallin chaperone activity may aid the development of therapeutic strategies that could evade the need for cataract surgery and revive lens transparency of the cataractous lenses. This article originally summarizes the significance of modulation and enhancing of α-crystallin chaperone activity with imidazole-containing dipeptides N-acetylcarnosine, carnosine and carcinine in consequence to prevent, delay or dissolve the human cataract. A growing evidence and discussion of recent patents are presented in this study that demonstrate the ability of N-acetylcarnosine (lubricant eye drops) or carcinine (lubricant eye drops) (universal antioxidant and deglycation agent) resistant to enzymatic hydrolysis with carnosinase to act as pharmacological chaperones, to decrease oxidative stress and ameliorate oxidative and excessive glycation stress-related eye disease phenotypes, suggesting that the field of chaperone therapy might hold novel treatments for age-related cataracts, age-related macular degeneration (AMD) and ocular complications of diabetes (OCD). The therapeutic strategies are highlighted in the study for identifying potential chaperone compounds and for experimentally demonstrating chaperone activity in in vitro and in vivo models of human age-related eye disease, such as cataracts and advanced glycation tissue proteins - engineered systems.

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Biological Activity of Novel Synthetic Derivatives of Carnosine

Cited by 43 publications

References 27 publications

Inhibitory effect of 2-arylbenzofurans from the Mori Cortex Radicis (Moraceae) on oxygen glucose deprivation (OGD)-induced cell death of SH-SY5Y cells

Inhibitory effect of 2-arylbenzofurans from the Mori Cortex Radicis (Moraceae) on oxygen glucose deprivation (OGD)-induced cell death of SH-SY5Y cells

Transforming dietary peptides in promising lead compounds: the case of bioavailable carnosine analogs

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