A new derivative of acetylsalicylic acid and carnosine: synthesis, physical and chemical properties, biological activity

• Published in: Daru Vol. 28; no. 1; pp. 119 - 130
• Main Authors: Kulikova, Olga I., Stvolinsky, Sergey L., Migulin, Vasily A., Andreeva, Ludmila A., Nagaev, Igor Yu, Lopacheva, Olga M., Kulichenkova, Ksenia N., Lopachev, Alexander V., Trubitsina, Irina E., Fedorova, Tatiana N.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.06.2020; BioMed Central Ltd
• Subjects: Acetic Acid; Analysis; Animals; Anti-Ulcer Agents - chemistry; Anti-Ulcer Agents - pharmacology; Anti-Ulcer Agents - therapeutic use; Antioxidants (Nutrients); Antioxidants - chemistry; Antioxidants - pharmacology; Antioxidants - therapeutic use; Aspirin; Aspirin - analogs & derivatives; Aspirin - chemistry; Aspirin - pharmacology; Aspirin - therapeutic use; Biomedical and Life Sciences; Biomedicine; Carnosine - analogs & derivatives; Carnosine - chemistry; Carnosine - pharmacology; Carnosine - therapeutic use; Chemical properties; Erythrocytes - drug effects; Gastrointestinal system; Hemolysis - drug effects; Humans; Hydrolysis; Instrument industry (Equipment); Leukocytes - drug effects; Male; Medicinal Chemistry; Organic acids; Pharmaceutical Sciences/Technology; Pharmacology/Toxicology; Phenols (Class of compounds); Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - chemistry; Platelet Aggregation Inhibitors - pharmacology; Platelet Aggregation Inhibitors - therapeutic use; Rats, Wistar; Research Article; Respiratory Burst - drug effects; Salicylates; Sodium hypochlorite; Stomach ulcer; Stomach Ulcer - chemically induced; Stomach Ulcer - drug therapy; Superoxides - chemistry; Time; United States; Russia; Antiplatelet action; Salicylic acid; Carnosine; Acetylsalicylic acid; Antioxidant; Gastrointestinal ulcer
• ISSN: 2008-2231; 1560-8115; 2008-2231
• DOI: 10.1007/s40199-019-00323-x

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 .