Olga I Kulikova1, Sergey L Stvolinsky2, Vasily A Migulin3, Ludmila A Andreeva4, Igor Yu Nagaev4, Olga M Lopacheva2, Ksenia N Kulichenkova2, Alexander V Lopachev2, Irina E Trubitsina5, Tatiana N Fedorova2. 1. Laboratory of Clinical and Experimental neurochemistry, Research Center of Neurology, Volokolamskoe shosse, 80, Moscow, Russian Federation, 125367. kulikova@neurology.ru. 2. Laboratory of Clinical and Experimental neurochemistry, Research Center of Neurology, Volokolamskoe shosse, 80, Moscow, Russian Federation, 125367. 3. N. D. Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences, Leninsky Prospect, 47, Moscow, Russian Federation, 119991. 4. Department of Chemistry of Physiologically Active Substances, Institute of Molecular Genetics of the Russian Academy of Sciences, Kurchatov Square 2, Moscow, Russian Federation, 123182. 5. Moscow Clinical Scientific Center after A.S. Loginov of the Moscow Healthcare Department, Shosse Enthusiasts, 86, Moscow, Russian Federation, 111125.
Abstract
PURPOSE: The aim of this study was to create and assess biological activity of a new compound based on carnosine and acetylsalicylic acid (ASA) that will comprise antioxidant effect with antiplatelet activity, while simultaneously preventing side effects on the gastrointestinal tract. METHODS: Salicyl-carnosine (SC) was synthesized by condensation of ASA and carnosine. Antioxidant activity was determined by spectrophotometric and chemiluminescence methods. Antiplatelet activity was carried out by the light transmission-aggregometry method using the inductor ADP. Chronic gastric ulcer in rats was modeled using glacial acetic acid. RESULTS: Using SOD-like activity, iron-induced chemiluminescence, BaSO4-activated respiratory burst, and evaluation of red blood cell structure stabilization during oxidative damage induced by sodium hypochlorite, it was shown that SC possesses antioxidant activity analogous, or better, than that of carnosine. Antiplatelet activity of SC was evaluated in the blood of healthy individuals, and was also shown to be comparable to, or exceeding that of ASA. Also SC demonstrates high resistance to hydrolysis by tissue and serum carnosinases. Most importantly, it was shown that SC has protected the gastric mucosa against the formation of stomach ulcerative lesions and promoted their epithelization, therefore overcoming the undesirable inherent side effects of ASA. CONCLUSIONS: SC preserves pharmacologically significant properties of ASA and carnosine while retaining an anti-ulcer activity and resistance to the carnosinase hydrolysis at the same time. These properties are particularly promising for the potential development of new anti-inflammatory and antithrombotic drugs. Graphical abstract .
PURPOSE: The aim of this study was to create and assess biological activity of a new compound based on carnosine and acetylsalicylic acid (ASA) that will comprise antioxidant effect with antiplatelet activity, while simultaneously preventing side effects on the gastrointestinal tract. METHODS:Salicyl-carnosine (SC) was synthesized by condensation of ASA and carnosine. Antioxidant activity was determined by spectrophotometric and chemiluminescence methods. Antiplatelet activity was carried out by the light transmission-aggregometry method using the inductor ADP. Chronic gastric ulcer in rats was modeled using glacial acetic acid. RESULTS: Using SOD-like activity, iron-induced chemiluminescence, BaSO4-activated respiratory burst, and evaluation of red blood cell structure stabilization during oxidative damage induced by sodium hypochlorite, it was shown that SC possesses antioxidant activity analogous, or better, than that of carnosine. Antiplatelet activity of SC was evaluated in the blood of healthy individuals, and was also shown to be comparable to, or exceeding that of ASA. Also SC demonstrates high resistance to hydrolysis by tissue and serum carnosinases. Most importantly, it was shown that SC has protected the gastric mucosa against the formation of stomach ulcerative lesions and promoted their epithelization, therefore overcoming the undesirable inherent side effects of ASA. CONCLUSIONS:SC preserves pharmacologically significant properties of ASA and carnosine while retaining an anti-ulcer activity and resistance to the carnosinase hydrolysis at the same time. These properties are particularly promising for the potential development of new anti-inflammatory and antithrombotic drugs. Graphical abstract .
Authors: S L Stvolinsky; E R Bulygina; T N Fedorova; K Meguro; T Sato; O V Tyulina; H Abe; A A Boldyrev Journal: Cell Mol Neurobiol Date: 2009-10-02 Impact factor: 5.046
Authors: S L Stvolinsky; N A Antonova; O I Kulikova; A V Lopachev; D A Abaimov; I Al-Baidani; O M Lopacheva; T N Fedorova; A P Kaplun; G M Sorokoumova Journal: Biomed Khim Date: 2018-06
Authors: Sean Bennet; Martin Kaufmann; Kaede Takami; Calvin Sjaarda; Katya Douchant; Emily Moslinger; Henry Wong; David E Reed; Anne K Ellis; Stephen Vanner; Robert I Colautti; Prameet M Sheth Journal: Sci Rep Date: 2022-06-15 Impact factor: 4.996