Free radical scavenging reactions of sulfasalazine, 5-aminosalicylic acid and sulfapyridine: Mechanistic aspects and antioxidant activity

R. Joshi, S. Kumar, M. Unnikrishnan, T. Mukherjee

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Reactions of sulfasalazine (SAZ) and its metabolites, 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP), with various oxidizing and reducing free radicals (hydroxyl, haloperoxyl, one-electron oxidizing, lipid peroxyl, glutathiyl, superoxide, tryptophanyl, etc.) have been studied to understand the mechanistic aspects of its action against free radicals produced during inflammation. Nanosecond pulse radiolysis technique coupled with transient spectrophotometry has been used for in situ generation of free radicals and to follow their reaction pathways. The transients produced in these reactions have been assigned and radical scavenging rate constants have been measured. In addition to scavenging of various primary and secondary free radicals by SAZ, 5-ASA and SP, 5-ASA has also been observed to efficiently scavenge radicals of biomolecules. 5-ASA has been found to be the active moiety of SAZ involved in the scavenging of oxidizing free radicals whereas reduction of SAZ produced molecular radical anion. The study suggests that free radical scavenging activity of 5-ASA may be a major path of pharmacological action of SAZ against inflammatory bowel diseases (IBD). © 2005 Taylor & Francis.
Original languageEnglish
Pages (from-to)1163-1172
Number of pages10
JournalFree Radical Research
Volume39
Issue number11
DOIs
Publication statusPublished - 2005
Externally publishedYes

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Sulfapyridine
Mesalamine
Sulfasalazine
Scavenging
Free Radicals
Antioxidants
Pulse Radiolysis
Radiolysis
Spectrophotometry
Biomolecules
Metabolites
Inflammatory Bowel Diseases
Superoxides
Hydroxyl Radical
Anions
Rate constants
Pharmacology
Electrons
Inflammation
Lipids

Cite this

@article{af26f52f40714d57b4ca9e691d9a8012,
title = "Free radical scavenging reactions of sulfasalazine, 5-aminosalicylic acid and sulfapyridine: Mechanistic aspects and antioxidant activity",
abstract = "Reactions of sulfasalazine (SAZ) and its metabolites, 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP), with various oxidizing and reducing free radicals (hydroxyl, haloperoxyl, one-electron oxidizing, lipid peroxyl, glutathiyl, superoxide, tryptophanyl, etc.) have been studied to understand the mechanistic aspects of its action against free radicals produced during inflammation. Nanosecond pulse radiolysis technique coupled with transient spectrophotometry has been used for in situ generation of free radicals and to follow their reaction pathways. The transients produced in these reactions have been assigned and radical scavenging rate constants have been measured. In addition to scavenging of various primary and secondary free radicals by SAZ, 5-ASA and SP, 5-ASA has also been observed to efficiently scavenge radicals of biomolecules. 5-ASA has been found to be the active moiety of SAZ involved in the scavenging of oxidizing free radicals whereas reduction of SAZ produced molecular radical anion. The study suggests that free radical scavenging activity of 5-ASA may be a major path of pharmacological action of SAZ against inflammatory bowel diseases (IBD). {\circledC} 2005 Taylor & Francis.",
author = "R. Joshi and S. Kumar and M. Unnikrishnan and T. Mukherjee",
note = "Cited By :51 Export Date: 10 November 2017 CODEN: FRARE Correspondence Address: Joshi, R.; Radiation Chemistry and Chemical Dynamics Division, Chemistry Group, Bhabha Atomic Research Center, Mumbai 400 085, India; email: rjudrin@yahoo.com Chemicals/CAS: mesalazine, 89-57-6; salazosulfapyridine, 599-79-1; sulfapyridine, 144-83-2; superoxide, 11062-77-4; Aminosalicylic Acids; Anions; Antioxidants; Free Radical Scavengers; Free Radicals; Glutathione, 70-18-8; Hydroxyl Radical, 3352-57-6; Mesalamine, 89-57-6; Oxygen, 7782-44-7; Peroxides; Sulfapyridine, 144-83-2; Sulfasalazine, 599-79-1; trichloromethylperoxy radical, 69884-58-8 Manufacturers: Sigma References: Azad-Khan, A.H., Piris, J., Truelove, S.C., An experiment to determine the active therapeutic moiety of sulfasalazine (1977) Lancet, 2, pp. 892-895; Ardizzone, S., Porro, G.B., A practical guide to the management of distal ulcerative colitis (1998) Drugs, 55, pp. 519-542; Babbs, C.F., Oxygen radicals in ulcerative colitis (1992) Free Radic. Biol. Med., 13, pp. 169-181; Shanhan, F., Targan, S., Inflammatory bowel disease: From bench to bedside (1994), Baltimore: Williams & Wilkens; Oyanagui, Y., Inhibition of superoxide anion production in macrophages by anti-inflammatory drugs (1976) Biochem. Pharmacol., 25, pp. 1473-1480; Hiller, K.O., Wilson, R.L., Hydroxyl free radicals and anti-inflammatory drugs: Biological inactivation studies and reaction rate constants (1983) Biochem. Pharmacol., 32, pp. 2109-2111; Peppercom, M.A., Goldman, P., The role of intestinal bacteria in the metabolism of salicylazosulfapyridine (1972) J. Pharm. Exp. Ther., 181, pp. 555-562; Miller, D.K., Gillard, J.W., Vickers, P.J., Sadowski, S., Leveille, C., Mancini, J.A., Charleson, P., Evans, J.F., Identification and isolation of a membrane protein necessary for leukotriene production (1990) Nature, 343, pp. 278-281; Packer, L., (1994) Methods in Enzymology, 234, pp. 555-572. , San Diego: Academic Press; Gionchetti, P., Guarnieri, C., Campieri, M., Belluzzi, A., Brignola, C., Iannoe, P., Miglioli, M., Barbara, L., Scavenger effects of sulfasalazine, 5-aminosalicylic acid, olsalazine on superoxide radical generation (1991) Dig. Dis. Sci., 36, pp. 174-178; Stevens, C., Lipman, M., Fabry, S., 5-Aminosalicylic acid abrogates T-cell proliferation by blocking interleukin 2 production in peripheral blood mononuclear cells (1995) J. Pharmacol. Exp. Ther., 272, pp. 399-406; Cominell, F., Zipser, C.A., Dinarello, C.A., Sulfasalazine inhibits cytokine production in human mononuclear cells: A novel anti-inflammatory mechanism (1992) Gastroentrology, 96, pp. A96; Pronai, L., Yukinobu, I., Lang, I., Feher, J., The oxygen centered radical scavenging activity of sulfasalazine and its metabolites. A direct protection of bowel (1992) Acta Physiol. Hung., 80, pp. 317-323; Yamada, T., Volkmer, C., Grisham, M.B., The effects of sulfasalazine metabolites on hemoglobin-catalyzed lipid peroxidation (1991) Free Radic. Biol. Med., 10, pp. 41-49; Baxendale, J.H., Busi, F., The study of fast processes and transient species by electron pulse radiolysis (1982), Dordrecht:. D. Riedel; Guha, S.N., Moorthy, P.N., Kishore, K., Naik, D.B., Rao, K.N., (1987) Proc. Ind. Acad. Sci. (Chem. Sci.), 99, pp. 261-271; Ahmad, S.A., (1997) Atomic, Molecular and Cluster Physics, , New Delhi: Narosa; Spinks, J.W.T., Woods, R.J., (1990) An Introduction to Radiation Chemistry, , New York: John Wiley; Buxton, G.V., Stuart, C.R., Re-evaluation of the thiocyanate dosimeter for pulse radiolysis (1995) J. Chem. Soc. Faraday Trans., 91, pp. 279-281; Buxton, G.V., Greenstock, C.L., Helman, W.P., Ross, A.B., Critical review of rate constants for reactions of the hydrated electrons, hydrogen atoms and hydroxyl radicals (OH/O ?) in aqueous solution (1988) J. Phys. Chem. Ref. Data, 17, pp. 513-886; Gordon, S., Schmidt, K.H., Hart, E.J., A pulse radiolysis study of aqueous benzene solutions (1977) J. Phys. Chem., 81, pp. 104-109; Alfassi, Z.B., Schuler, R.H., Reaction of azide radicals with aromatic compounds. Azide as a selective oxidant (1985) J. Phys. Chem., 89, pp. 3359-3363; Aruoma, O.I., Wasil, M., Halliwell, B., Hoey, B.M., Butler, J., The scavenging of oxidants by sulfasalazine and its metabolites. A possible contribution to their anti-inflammatory effects? (1987) Biochem. Pharmacol., 36, pp. 3739-3742; Motahashi, N., Saito, Y., Rate constants for reaction of hydroxyl radicals with sulfapyridine and aminosalicylic acid (1996) Chem. Pharm. Bull., 44, pp. 163-166; Solar, S., Getoff, N., Sehested, K., Holcman, J., Pulse radiolysis of pyridine carboxylic acids in aqueous solution (1991) Radiat. Phys. Chem., 38, pp. 323-332; Joshi, R., Kapoor, S., Mukherjee, T., Free radical reactions of pyridoxal (vitamin B6): A pulse radiolysis study (2002) Res. Chem. Intermed., 28, pp. 505-515; Das, T.N., Dhanasekaran, T., Alfassi, Z.B., Neta, P., Reduction potential of the tert-butyl peroxyl radical in aqueous solutions (1998) J. Phys. Chem. A., 102, pp. 280-284; Neta, P., Huie, R.E., Ross, A.B., Rate constants for reactions of peroxyl radicals in fluid solutions (1990) J. Phys. Chem. Ref. Data, 19, pp. 413-513; Packer, J.E., Slater, T.F., Wilson, R.L., Direct observation of a free radical interaction between vitamin E and C (1979) Nature, 278, pp. 737-738; Allgayer, H., Hofer, P., Schmidt, M., Bohne, P., Kruis, W., Gugler, R., Superoxide, hydroxyl and fatty acid radical scavenging by aminosalicylate. Direct evaluation with electron spin resonance spectroscopy (1992) Biochem. Pharmacol., 43, pp. 259-262; Kimura, I., Kumamoto, T., Matsuda, A., Katoka, M., Kokuba, Y., Effects of BX661A, a new therapeutic agent for ulcerative colitis, on reactive oxygen species in comparison with salazosulfapyridine and its metabolite sulfapyridine (1998) Arjzneimittel-Forschung, 48, pp. 1007-1011; Joshi, R., Mukherjee, T., Charge transfer between tryptophan and tyrosine in casein: A pulse radiolysis study (2002) Biophys. Chem., 96, pp. 15-19; Joshi, R., Mukherjee, T., Effect of solvent viscosity, polarity and pH on the charge transfer between tryptophan radical and tyrosine in bovine serum albumin: A pulse radiolysis study (2002) Biophys. Chem., 103, pp. 89-98; Sch{\"o}neich, C., Asmus, K.-D., Reaction of thiyl radicals with alcohols, ethers and polyunsaturated fatty acids: A possible role of thiyl radicals in thiol mutagenesis? (1990) Radiat. Environ. Biophys., 29, pp. 263-271; Stocker, R., Frei, B., Endogenous antioxidant defences in human blood plasma (1991) Oxidative Stress: Oxidants and Antioxidants, pp. 213-243. , Sies H, editor. London: Academic Press; Sch{\"o}neich, C., Dillinger, U., von Bruchhausen, F., Asmus, K.-D., Oxidation of polyunsaturated fatty acids and lipids through thiyl and sulfonyl radicals: Reaction kinetics and influence of oxygen and structure of thiyl radicals (1992) Arch. Biochem. Biophys., 292, pp. 456-467; Surdhar, S.P., Armstrong, D., Reduction potential and exchange reactions of thiyl radicals and disulfide anion radicals (1987) J. Phys. Chem., 91, pp. 6532-6537; Pr{\"u}tz, W.A., Butler, J., Land, E.J., The glutathione free radical equilibrium, GS.+GS- ⇔ GSSG.-, mediating electron transfer to Fe(III)-cytochrome c (1994) Biophys. Chem., 49, pp. 101-110; Schuler, R.H., Oxidation of ascorbate anion by electron transfer to phenoxyl radicals (1977) Radiat. Res., 69, pp. 417-433",
year = "2005",
doi = "10.1080/10715760500177880",
language = "English",
volume = "39",
pages = "1163--1172",
journal = "Free Radical Research",
issn = "1071-5762",
publisher = "Informa Healthcare",
number = "11",

}

Free radical scavenging reactions of sulfasalazine, 5-aminosalicylic acid and sulfapyridine: Mechanistic aspects and antioxidant activity. / Joshi, R.; Kumar, S.; Unnikrishnan, M.; Mukherjee, T.

In: Free Radical Research, Vol. 39, No. 11, 2005, p. 1163-1172.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Free radical scavenging reactions of sulfasalazine, 5-aminosalicylic acid and sulfapyridine: Mechanistic aspects and antioxidant activity

AU - Joshi, R.

AU - Kumar, S.

AU - Unnikrishnan, M.

AU - Mukherjee, T.

N1 - Cited By :51 Export Date: 10 November 2017 CODEN: FRARE Correspondence Address: Joshi, R.; Radiation Chemistry and Chemical Dynamics Division, Chemistry Group, Bhabha Atomic Research Center, Mumbai 400 085, India; email: rjudrin@yahoo.com Chemicals/CAS: mesalazine, 89-57-6; salazosulfapyridine, 599-79-1; sulfapyridine, 144-83-2; superoxide, 11062-77-4; Aminosalicylic Acids; Anions; Antioxidants; Free Radical Scavengers; Free Radicals; Glutathione, 70-18-8; Hydroxyl Radical, 3352-57-6; Mesalamine, 89-57-6; Oxygen, 7782-44-7; Peroxides; Sulfapyridine, 144-83-2; Sulfasalazine, 599-79-1; trichloromethylperoxy radical, 69884-58-8 Manufacturers: Sigma References: Azad-Khan, A.H., Piris, J., Truelove, S.C., An experiment to determine the active therapeutic moiety of sulfasalazine (1977) Lancet, 2, pp. 892-895; Ardizzone, S., Porro, G.B., A practical guide to the management of distal ulcerative colitis (1998) Drugs, 55, pp. 519-542; Babbs, C.F., Oxygen radicals in ulcerative colitis (1992) Free Radic. Biol. Med., 13, pp. 169-181; Shanhan, F., Targan, S., Inflammatory bowel disease: From bench to bedside (1994), Baltimore: Williams & Wilkens; Oyanagui, Y., Inhibition of superoxide anion production in macrophages by anti-inflammatory drugs (1976) Biochem. Pharmacol., 25, pp. 1473-1480; Hiller, K.O., Wilson, R.L., Hydroxyl free radicals and anti-inflammatory drugs: Biological inactivation studies and reaction rate constants (1983) Biochem. Pharmacol., 32, pp. 2109-2111; Peppercom, M.A., Goldman, P., The role of intestinal bacteria in the metabolism of salicylazosulfapyridine (1972) J. Pharm. Exp. Ther., 181, pp. 555-562; Miller, D.K., Gillard, J.W., Vickers, P.J., Sadowski, S., Leveille, C., Mancini, J.A., Charleson, P., Evans, J.F., Identification and isolation of a membrane protein necessary for leukotriene production (1990) Nature, 343, pp. 278-281; Packer, L., (1994) Methods in Enzymology, 234, pp. 555-572. , San Diego: Academic Press; Gionchetti, P., Guarnieri, C., Campieri, M., Belluzzi, A., Brignola, C., Iannoe, P., Miglioli, M., Barbara, L., Scavenger effects of sulfasalazine, 5-aminosalicylic acid, olsalazine on superoxide radical generation (1991) Dig. Dis. Sci., 36, pp. 174-178; Stevens, C., Lipman, M., Fabry, S., 5-Aminosalicylic acid abrogates T-cell proliferation by blocking interleukin 2 production in peripheral blood mononuclear cells (1995) J. Pharmacol. Exp. Ther., 272, pp. 399-406; Cominell, F., Zipser, C.A., Dinarello, C.A., Sulfasalazine inhibits cytokine production in human mononuclear cells: A novel anti-inflammatory mechanism (1992) Gastroentrology, 96, pp. A96; Pronai, L., Yukinobu, I., Lang, I., Feher, J., The oxygen centered radical scavenging activity of sulfasalazine and its metabolites. A direct protection of bowel (1992) Acta Physiol. Hung., 80, pp. 317-323; Yamada, T., Volkmer, C., Grisham, M.B., The effects of sulfasalazine metabolites on hemoglobin-catalyzed lipid peroxidation (1991) Free Radic. Biol. Med., 10, pp. 41-49; Baxendale, J.H., Busi, F., The study of fast processes and transient species by electron pulse radiolysis (1982), Dordrecht:. D. Riedel; Guha, S.N., Moorthy, P.N., Kishore, K., Naik, D.B., Rao, K.N., (1987) Proc. Ind. Acad. Sci. (Chem. Sci.), 99, pp. 261-271; Ahmad, S.A., (1997) Atomic, Molecular and Cluster Physics, , New Delhi: Narosa; Spinks, J.W.T., Woods, R.J., (1990) An Introduction to Radiation Chemistry, , New York: John Wiley; Buxton, G.V., Stuart, C.R., Re-evaluation of the thiocyanate dosimeter for pulse radiolysis (1995) J. Chem. Soc. Faraday Trans., 91, pp. 279-281; Buxton, G.V., Greenstock, C.L., Helman, W.P., Ross, A.B., Critical review of rate constants for reactions of the hydrated electrons, hydrogen atoms and hydroxyl radicals (OH/O ?) in aqueous solution (1988) J. Phys. Chem. Ref. Data, 17, pp. 513-886; Gordon, S., Schmidt, K.H., Hart, E.J., A pulse radiolysis study of aqueous benzene solutions (1977) J. Phys. Chem., 81, pp. 104-109; Alfassi, Z.B., Schuler, R.H., Reaction of azide radicals with aromatic compounds. Azide as a selective oxidant (1985) J. Phys. Chem., 89, pp. 3359-3363; Aruoma, O.I., Wasil, M., Halliwell, B., Hoey, B.M., Butler, J., The scavenging of oxidants by sulfasalazine and its metabolites. A possible contribution to their anti-inflammatory effects? (1987) Biochem. Pharmacol., 36, pp. 3739-3742; Motahashi, N., Saito, Y., Rate constants for reaction of hydroxyl radicals with sulfapyridine and aminosalicylic acid (1996) Chem. Pharm. Bull., 44, pp. 163-166; Solar, S., Getoff, N., Sehested, K., Holcman, J., Pulse radiolysis of pyridine carboxylic acids in aqueous solution (1991) Radiat. Phys. Chem., 38, pp. 323-332; Joshi, R., Kapoor, S., Mukherjee, T., Free radical reactions of pyridoxal (vitamin B6): A pulse radiolysis study (2002) Res. Chem. Intermed., 28, pp. 505-515; Das, T.N., Dhanasekaran, T., Alfassi, Z.B., Neta, P., Reduction potential of the tert-butyl peroxyl radical in aqueous solutions (1998) J. Phys. Chem. A., 102, pp. 280-284; Neta, P., Huie, R.E., Ross, A.B., Rate constants for reactions of peroxyl radicals in fluid solutions (1990) J. Phys. Chem. Ref. Data, 19, pp. 413-513; Packer, J.E., Slater, T.F., Wilson, R.L., Direct observation of a free radical interaction between vitamin E and C (1979) Nature, 278, pp. 737-738; Allgayer, H., Hofer, P., Schmidt, M., Bohne, P., Kruis, W., Gugler, R., Superoxide, hydroxyl and fatty acid radical scavenging by aminosalicylate. Direct evaluation with electron spin resonance spectroscopy (1992) Biochem. Pharmacol., 43, pp. 259-262; Kimura, I., Kumamoto, T., Matsuda, A., Katoka, M., Kokuba, Y., Effects of BX661A, a new therapeutic agent for ulcerative colitis, on reactive oxygen species in comparison with salazosulfapyridine and its metabolite sulfapyridine (1998) Arjzneimittel-Forschung, 48, pp. 1007-1011; Joshi, R., Mukherjee, T., Charge transfer between tryptophan and tyrosine in casein: A pulse radiolysis study (2002) Biophys. Chem., 96, pp. 15-19; Joshi, R., Mukherjee, T., Effect of solvent viscosity, polarity and pH on the charge transfer between tryptophan radical and tyrosine in bovine serum albumin: A pulse radiolysis study (2002) Biophys. Chem., 103, pp. 89-98; Schöneich, C., Asmus, K.-D., Reaction of thiyl radicals with alcohols, ethers and polyunsaturated fatty acids: A possible role of thiyl radicals in thiol mutagenesis? (1990) Radiat. Environ. Biophys., 29, pp. 263-271; Stocker, R., Frei, B., Endogenous antioxidant defences in human blood plasma (1991) Oxidative Stress: Oxidants and Antioxidants, pp. 213-243. , Sies H, editor. London: Academic Press; Schöneich, C., Dillinger, U., von Bruchhausen, F., Asmus, K.-D., Oxidation of polyunsaturated fatty acids and lipids through thiyl and sulfonyl radicals: Reaction kinetics and influence of oxygen and structure of thiyl radicals (1992) Arch. Biochem. Biophys., 292, pp. 456-467; Surdhar, S.P., Armstrong, D., Reduction potential and exchange reactions of thiyl radicals and disulfide anion radicals (1987) J. Phys. Chem., 91, pp. 6532-6537; Prütz, W.A., Butler, J., Land, E.J., The glutathione free radical equilibrium, GS.+GS- ⇔ GSSG.-, mediating electron transfer to Fe(III)-cytochrome c (1994) Biophys. Chem., 49, pp. 101-110; Schuler, R.H., Oxidation of ascorbate anion by electron transfer to phenoxyl radicals (1977) Radiat. Res., 69, pp. 417-433

PY - 2005

Y1 - 2005

N2 - Reactions of sulfasalazine (SAZ) and its metabolites, 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP), with various oxidizing and reducing free radicals (hydroxyl, haloperoxyl, one-electron oxidizing, lipid peroxyl, glutathiyl, superoxide, tryptophanyl, etc.) have been studied to understand the mechanistic aspects of its action against free radicals produced during inflammation. Nanosecond pulse radiolysis technique coupled with transient spectrophotometry has been used for in situ generation of free radicals and to follow their reaction pathways. The transients produced in these reactions have been assigned and radical scavenging rate constants have been measured. In addition to scavenging of various primary and secondary free radicals by SAZ, 5-ASA and SP, 5-ASA has also been observed to efficiently scavenge radicals of biomolecules. 5-ASA has been found to be the active moiety of SAZ involved in the scavenging of oxidizing free radicals whereas reduction of SAZ produced molecular radical anion. The study suggests that free radical scavenging activity of 5-ASA may be a major path of pharmacological action of SAZ against inflammatory bowel diseases (IBD). © 2005 Taylor & Francis.

AB - Reactions of sulfasalazine (SAZ) and its metabolites, 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP), with various oxidizing and reducing free radicals (hydroxyl, haloperoxyl, one-electron oxidizing, lipid peroxyl, glutathiyl, superoxide, tryptophanyl, etc.) have been studied to understand the mechanistic aspects of its action against free radicals produced during inflammation. Nanosecond pulse radiolysis technique coupled with transient spectrophotometry has been used for in situ generation of free radicals and to follow their reaction pathways. The transients produced in these reactions have been assigned and radical scavenging rate constants have been measured. In addition to scavenging of various primary and secondary free radicals by SAZ, 5-ASA and SP, 5-ASA has also been observed to efficiently scavenge radicals of biomolecules. 5-ASA has been found to be the active moiety of SAZ involved in the scavenging of oxidizing free radicals whereas reduction of SAZ produced molecular radical anion. The study suggests that free radical scavenging activity of 5-ASA may be a major path of pharmacological action of SAZ against inflammatory bowel diseases (IBD). © 2005 Taylor & Francis.

U2 - 10.1080/10715760500177880

DO - 10.1080/10715760500177880

M3 - Article

VL - 39

SP - 1163

EP - 1172

JO - Free Radical Research

JF - Free Radical Research

SN - 1071-5762

IS - 11

ER -