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

Publisher: Springer International Publishing Country of Publication: Switzerland NLM ID: 101125969 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2008-2231 (Electronic) Linking ISSN: 15608115 NLM ISO Abbreviation: Daru Subsets: MEDLINE

Publication: 2018- : Cham : Springer International Publishing
Original Publication: Tehran, Iran : The Faculty

Anti-Ulcer Agents*/chemistry ; Anti-Ulcer Agents*/pharmacology ; Anti-Ulcer Agents*/therapeutic use ; Antioxidants*/chemistry ; Antioxidants*/pharmacology ; Antioxidants*/therapeutic use ; Aspirin*/analogs & derivatives ; Aspirin*/chemistry ; Aspirin*/pharmacology ; Aspirin*/therapeutic use ; Carnosine*/analogs & derivatives ; Carnosine*/chemistry ; Carnosine*/pharmacology ; Carnosine*/therapeutic use ; Platelet Aggregation Inhibitors*/chemistry ; Platelet Aggregation Inhibitors*/pharmacology ; Platelet Aggregation Inhibitors*/therapeutic use; Acetic Acid ; Animals ; Erythrocytes/drug effects ; Hemolysis/drug effects ; Humans ; Hydrolysis ; Leukocytes/drug effects ; Male ; Platelet Aggregation/drug effects ; Rats, Wistar ; Respiratory Burst/drug effects ; Stomach Ulcer/chemically induced ; Stomach Ulcer/drug therapy ; Superoxides/chemistry

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 .

Annu Rev Phytopathol. 2009;47:177-206. (PMID: 19400653)
Free Radic Res Commun. 1991;12-13 Pt 1:179-85. (PMID: 1649087)
Cell Mol Neurobiol. 2010 Apr;30(3):395-404. (PMID: 19798566)
J Biol Chem. 1981 Feb 25;256(4):1910-4. (PMID: 6257693)
Biomed Khim. 2018 Jun;64(3):268-275. (PMID: 29964264)
Cochrane Database Syst Rev. 2017 Feb 28;2:CD009493. (PMID: 28245346)
Xenobiotica. 1988 Apr;18(4):459-70. (PMID: 3135672)
Expert Opin Ther Pat. 2011 Dec;21(12):1831-41. (PMID: 22098318)
J Pharm Sci. 1967 Oct;56(10):1261-6. (PMID: 6059444)
Free Radic Res Commun. 1991;14(4):289-96. (PMID: 1874458)
Dig Dis Sci. 1998 Sep;43(9):2003-11. (PMID: 9753266)
Free Radic Biol Med. 1993 Mar;14(3):303-11. (PMID: 8458588)
Annu Rev Biochem. 1980;49:695-726. (PMID: 6250449)
Free Radic Res. 2005 Nov;39(11):1163-72. (PMID: 16298742)
Biokhimiia. 1987 Jul;52(7):1216-20. (PMID: 2822148)
Mol Cell Biochem. 1999 Sep;199(1-2):93-102. (PMID: 10544957)
Nature. 1967 Jul 22;215(5099):413-4. (PMID: 6058303)
Free Radic Res. 1997 Oct;27(4):419-27. (PMID: 9416470)
Pharmacol Rev. 2018 Jul;70(3):526-548. (PMID: 29925522)
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2019 Jan 28;44(1):22-27. (PMID: 30837398)
Nature. 1962 Jun 9;194:927-9. (PMID: 13871375)
Comp Biochem Physiol B Biochem Mol Biol. 1995 Nov;112(3):481-5. (PMID: 8529024)
Patol Fiziol Eksp Ter. 1997 Oct-Dec;(4):17-20. (PMID: 9471595)
Vopr Med Khim. 1995 Jan-Feb;41(1):41-3. (PMID: 7771091)
Vet Res Commun. 2012 Mar;36(1):29-33. (PMID: 22012073)
Ther Clin Risk Manag. 2015 Sep 24;11:1449-56. (PMID: 26445544)
Alcohol Alcohol. 2000 Jan;35(1):44-8. (PMID: 10684775)
PLoS One. 2014 Jun 03;9(6):e98513. (PMID: 24892779)
Amino Acids. 2019 Jan;51(1):139-150. (PMID: 30353356)
Curr Med Chem. 2011;18(21):3252-64. (PMID: 21671857)
Dig Dis Sci. 2001 Apr;46(4):845-51. (PMID: 11330422)
J Pharmacol Sci. 2009 Jul;110(3):285-94. (PMID: 19542683)
Am J Dig Dis. 1971 Mar;16(3):277-84. (PMID: 5554507)
Comp Biochem Physiol B Biochem Mol Biol. 2000 Dec;127(4):443-6. (PMID: 11281261)
Physiol Rev. 2013 Oct;93(4):1803-45. (PMID: 24137022)
Redox Rep. 2010;15(6):259-67. (PMID: 21208525)
Nat New Biol. 1971 Jun 23;231(25):232-5. (PMID: 5284360)
Biochemistry. 2006 Jul 4;45(26):8152-62. (PMID: 16800640)
Circulation. 2000 Mar 14;101(10):1206-18. (PMID: 10715270)
Hum Exp Toxicol. 2001 Jan;20(1):34-7. (PMID: 11339623)

Keywords: Acetylsalicylic acid; Antioxidant; Antiplatelet action; Carnosine; Gastrointestinal ulcer; Salicylic acid

0 (Anti-Ulcer Agents)
0 (Antioxidants)
0 (Platelet Aggregation Inhibitors)
11062-77-4 (Superoxides)
8HO6PVN24W (Carnosine)
Q40Q9N063P (Acetic Acid)
R16CO5Y76E (Aspirin)

Date Created: 20200106 Date Completed: 20210226 Latest Revision: 20210226

20231215

PMC7214588

10.1007/s40199-019-00323-x

31902097