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İlaç Hammaddesi Olarak Sentezlenen Elektrofilik ve Nonelektrofilik Fenolik Schiff Bazlarının Umu Test Sistemi ile Genotoksik Aktivitesinin Araştırılması

Year 2010, Volume: 7 Issue: 2, - , 01.04.2010

Abstract

In this work, we investigated, through a short-term genotoxicity experiment,
the umu-test, the mutagenic activities of a group of phenolic Schiff bases, namely Material
A 2-(N-phenyliminomethyl)-phenol, Material B 2-(N-p-bromophenyliminomethyl)-
phenol, Material C 2-(N-p-methylphenyliminomethyl)-phenol and Material D 2-(N-panilinephenyl
iminomethyl)-phenol, the substances which we synthesized, in the chemistry
laboratories of our university, to form the raw materials of medicines. The umu-test
method is a colorimetric bacterial test system and has been developed on the basis of SOS
response induced by DNA damage. Materials A, B, C and D and the experimental materials
prepared in 5 different dose levels by dissolving these materials in DMSO have not
increased the galactosidase enzyme activity. When calculated with respect to the enzyme
unit calculation formula, results seemed to be not larger than the unit value of the positive
mutagenic material 4NQO. Results have also been evaluated statistically.

References

  • [1] H. Bagci, J. H. Stuy, Bromouracil-induced mutagenesis in a mismatch-repair-deficient strain of Haemophilus influenzae, Mutat. Res. 73 (1994), 15–19.
  • [2] P. Quillardet and M. Hofnung, The SOS Chromotest, a colorimetric bacterial assay for genotoxins: procedures, Mutat. Res. 147 (1985), 65–78.
  • [3] D. Forman, Ames, the Ames test, and the causes of cancer, BMJ 303 (1991), 428–429.
  • [4] B. N. Ames, Mutagenesis and carcinogenesis: Endogenous and exogenous factors, Environ. Mol. Mutagen. 14 (1989), 66–77.
  • [5] P. Einist¨o, M. Watanabe, M. Jr. Ishidate, T. Nohmi, Mutagenicity of 30 chemicals in Salmonella typhimurium strains possessing different nitroreductase or O-acetyltransferase activities, Mutat. Res. 259 (1991), 95–102.
  • [6] R. Vikse, A. Knapstad, L. Klungsøyr and S. Grivas, Mutagenic activity of the methyl and phenyl derivatives of the food mutagen 2-amino-3-methylimidazo[4,5-f]quinoxaline (IQx) in the Ames test, Mutat. Res. 298 (1993), 207–214.
  • [7] M. Manneberg, W. Lahm and M. Fountoulakis, Quantification of cysteine residues following oxidation to cysteic acid in the presence of sodium azide, Anal. Biochem. 231 (1995), 349–353.
  • [8] J. S. Fisherman, B. L. Osborn, H. G. Chun, J. Plowman, A. C. Smith, M. C. Christian, D. S. Zaharko and R. H. Shoemaker, Chloroquinoxaline sulfonamide: A sulfanilamide antitumor agent entering clinical trials, Invest. New Drugs 11 (1993), 1–9.
  • [9] N. S. Habib and S. A. el-Hawash, Synthesis and antimicrobial testing of thiazolinyl-, thiazolidinonyl-quinoxalines and 1,2,4-triazolo[4,3-a]quinoxalines, Pharmazie 52 (1997), 594–598.
  • [10] J. B. Sutherland, F. E. Evans, J. P. Freeman and A. J. Williams, Biotransformation of quinoxaline by Streptomyces badius, Lett. Appl. Microbiol. 22 (1996), 199–201.
  • [11] Y. Oda, H. Yamazaki, M. Watanabe, T. Nohmi and T. Shimada, Highly sensitive umu test system for the detection of mutagenic nitroarenes in Salmonella typhimurium NM3009 having high O-acetyltransferase and nitroreductase activities, Environ. Mol. Mutagen. 21 (1993), 357–364.
  • [12] Y. Oda, H. Yamazaki and T. Shimada, Role of human N-acetyltransferases, NAT1 or NAT2, in genotoxicity of nitroarenes and aromatic amines in Salmonella typhimurium NM6001 and NM6002, Carcinogenesis 20 (1999), 1079–1083.
  • [13] Y. Oda, H. Yamazaki, M. Watanabe, T. Nohmi and T. Shimada, Development of high sensitive umu test system: rapid detection of genotoxicity of promutagenic aromatic amines by Salmonella typhimurium strain NM2009 possessing high O-acetyltransferase activity, Mutat. Res. 334 (1995), 145–156.
  • [14] G. Reifferscheid and J. Heil, Validation of the SOS/umu test using test results of 486 chemicals and comparison with the Ames test and carcinogenicity data, Mutat. Res. 369 (1996), 129– 145.
  • [15] D. W. Hein, M. Hirata, I. B. Glowinski and W. W. Weber, Biochemical evidence for the coexistence of monomorphic and polymorphic N-acetyltransferase activities on a common protein in rabbit liver, J. Pharmacol. Exp. Ther. 220 (1982), 1–7.
  • [16] O. H. Lowry, N. J. Rosenbrough, A. L. Farr and R. J. Randall, Protein measurement with the Folin phenol reagent, J. Biol. Chem. 193 (1951), 265–275.
  • [17] K. T. Bogen, Applicability of alternative models of revertant variance to Ames-test data for 121 mutagenic carcinogens, Mutat. Res. 322 (1994), 265–273.
  • [18] L. Dalgaard, R. K. Hjortkjaer, B. Regnier and L. Nordholm, Pharmacokinetics of the neuroprotective glutamate antagonist NBQX (6-nitro-7-sulfamoyl-benzo(f)quinoxaline-2,3-dione) in mice, rats, and dogs. Interactions with probenecid, Drug Metab. Dispos. 22 (1994), 289–293.
  • [19] C. Sengstag C and F. E. W¨urgler, DNA recombination induced by aflatoxin B1 activated by cytochrome P450 1A enzymes, Mol. Carcinog. 11 (1994), 227–235.
  • [20] N. Shibuya, T. Ohta, H. Nakadaira, H. Mano, K. Endoh and M. Yamamoto, Mutagenicity of activated carbon adsorbate of drinking water in the Ames assay, Tohoku J. Exp. Med. 171 (1993), 89–95.
  • [21] L. D. Claxton, J. Creason, B. Leroux, E. Agurell, S. Bagley, D. W. Bryant, Y. A. Courtois, G. Douglas, C. B. Clare, S. Goto, P. Quillardet, D. R. Jagannath, K. Kataoka, G. Mohn, P. A. Nielsen, T. Ong, T. C. Pederson, H. Shimizu, L. Nylund, H. Tokiwa, G. J. Vink, Y. Wang and D. Warshawsky, Results of the IPCS collaborative study on complex mixtures, Mutat. Res. 276 (1992), 23–32.
  • [22] S. Monarca, R. Pasquini and P. Arcaleni, Detection of mutagens in unconcentrated and concentrated drinking water supplies before and after treatment using a microscale fluctuation test, Chemosphere 14 (1985), 1069–1080.
  • [23] M. Font, A. Monge, E. Alvarez, A. Cuartero, M. J. Losa, M. J. Fidalgo, C. SanMart´ın, E. Nadal, I. Ruiz, I. Merino, J. J. Mart´ınez-Irujo, E. Alberdi, E. Santiago, I. Prieto, J. J. Lasarte, P. Sarobe and F. Borr´as, Synthesis and evaluation of new Reissert analogs as HIV-1 reverse transcriptase inhibitors. 1. Quinoline and quinoxaline derivatives, Drug Des. Discov. 14 (1997), 305–332.
Year 2010, Volume: 7 Issue: 2, - , 01.04.2010

Abstract

References

  • [1] H. Bagci, J. H. Stuy, Bromouracil-induced mutagenesis in a mismatch-repair-deficient strain of Haemophilus influenzae, Mutat. Res. 73 (1994), 15–19.
  • [2] P. Quillardet and M. Hofnung, The SOS Chromotest, a colorimetric bacterial assay for genotoxins: procedures, Mutat. Res. 147 (1985), 65–78.
  • [3] D. Forman, Ames, the Ames test, and the causes of cancer, BMJ 303 (1991), 428–429.
  • [4] B. N. Ames, Mutagenesis and carcinogenesis: Endogenous and exogenous factors, Environ. Mol. Mutagen. 14 (1989), 66–77.
  • [5] P. Einist¨o, M. Watanabe, M. Jr. Ishidate, T. Nohmi, Mutagenicity of 30 chemicals in Salmonella typhimurium strains possessing different nitroreductase or O-acetyltransferase activities, Mutat. Res. 259 (1991), 95–102.
  • [6] R. Vikse, A. Knapstad, L. Klungsøyr and S. Grivas, Mutagenic activity of the methyl and phenyl derivatives of the food mutagen 2-amino-3-methylimidazo[4,5-f]quinoxaline (IQx) in the Ames test, Mutat. Res. 298 (1993), 207–214.
  • [7] M. Manneberg, W. Lahm and M. Fountoulakis, Quantification of cysteine residues following oxidation to cysteic acid in the presence of sodium azide, Anal. Biochem. 231 (1995), 349–353.
  • [8] J. S. Fisherman, B. L. Osborn, H. G. Chun, J. Plowman, A. C. Smith, M. C. Christian, D. S. Zaharko and R. H. Shoemaker, Chloroquinoxaline sulfonamide: A sulfanilamide antitumor agent entering clinical trials, Invest. New Drugs 11 (1993), 1–9.
  • [9] N. S. Habib and S. A. el-Hawash, Synthesis and antimicrobial testing of thiazolinyl-, thiazolidinonyl-quinoxalines and 1,2,4-triazolo[4,3-a]quinoxalines, Pharmazie 52 (1997), 594–598.
  • [10] J. B. Sutherland, F. E. Evans, J. P. Freeman and A. J. Williams, Biotransformation of quinoxaline by Streptomyces badius, Lett. Appl. Microbiol. 22 (1996), 199–201.
  • [11] Y. Oda, H. Yamazaki, M. Watanabe, T. Nohmi and T. Shimada, Highly sensitive umu test system for the detection of mutagenic nitroarenes in Salmonella typhimurium NM3009 having high O-acetyltransferase and nitroreductase activities, Environ. Mol. Mutagen. 21 (1993), 357–364.
  • [12] Y. Oda, H. Yamazaki and T. Shimada, Role of human N-acetyltransferases, NAT1 or NAT2, in genotoxicity of nitroarenes and aromatic amines in Salmonella typhimurium NM6001 and NM6002, Carcinogenesis 20 (1999), 1079–1083.
  • [13] Y. Oda, H. Yamazaki, M. Watanabe, T. Nohmi and T. Shimada, Development of high sensitive umu test system: rapid detection of genotoxicity of promutagenic aromatic amines by Salmonella typhimurium strain NM2009 possessing high O-acetyltransferase activity, Mutat. Res. 334 (1995), 145–156.
  • [14] G. Reifferscheid and J. Heil, Validation of the SOS/umu test using test results of 486 chemicals and comparison with the Ames test and carcinogenicity data, Mutat. Res. 369 (1996), 129– 145.
  • [15] D. W. Hein, M. Hirata, I. B. Glowinski and W. W. Weber, Biochemical evidence for the coexistence of monomorphic and polymorphic N-acetyltransferase activities on a common protein in rabbit liver, J. Pharmacol. Exp. Ther. 220 (1982), 1–7.
  • [16] O. H. Lowry, N. J. Rosenbrough, A. L. Farr and R. J. Randall, Protein measurement with the Folin phenol reagent, J. Biol. Chem. 193 (1951), 265–275.
  • [17] K. T. Bogen, Applicability of alternative models of revertant variance to Ames-test data for 121 mutagenic carcinogens, Mutat. Res. 322 (1994), 265–273.
  • [18] L. Dalgaard, R. K. Hjortkjaer, B. Regnier and L. Nordholm, Pharmacokinetics of the neuroprotective glutamate antagonist NBQX (6-nitro-7-sulfamoyl-benzo(f)quinoxaline-2,3-dione) in mice, rats, and dogs. Interactions with probenecid, Drug Metab. Dispos. 22 (1994), 289–293.
  • [19] C. Sengstag C and F. E. W¨urgler, DNA recombination induced by aflatoxin B1 activated by cytochrome P450 1A enzymes, Mol. Carcinog. 11 (1994), 227–235.
  • [20] N. Shibuya, T. Ohta, H. Nakadaira, H. Mano, K. Endoh and M. Yamamoto, Mutagenicity of activated carbon adsorbate of drinking water in the Ames assay, Tohoku J. Exp. Med. 171 (1993), 89–95.
  • [21] L. D. Claxton, J. Creason, B. Leroux, E. Agurell, S. Bagley, D. W. Bryant, Y. A. Courtois, G. Douglas, C. B. Clare, S. Goto, P. Quillardet, D. R. Jagannath, K. Kataoka, G. Mohn, P. A. Nielsen, T. Ong, T. C. Pederson, H. Shimizu, L. Nylund, H. Tokiwa, G. J. Vink, Y. Wang and D. Warshawsky, Results of the IPCS collaborative study on complex mixtures, Mutat. Res. 276 (1992), 23–32.
  • [22] S. Monarca, R. Pasquini and P. Arcaleni, Detection of mutagens in unconcentrated and concentrated drinking water supplies before and after treatment using a microscale fluctuation test, Chemosphere 14 (1985), 1069–1080.
  • [23] M. Font, A. Monge, E. Alvarez, A. Cuartero, M. J. Losa, M. J. Fidalgo, C. SanMart´ın, E. Nadal, I. Ruiz, I. Merino, J. J. Mart´ınez-Irujo, E. Alberdi, E. Santiago, I. Prieto, J. J. Lasarte, P. Sarobe and F. Borr´as, Synthesis and evaluation of new Reissert analogs as HIV-1 reverse transcriptase inhibitors. 1. Quinoline and quinoxaline derivatives, Drug Des. Discov. 14 (1997), 305–332.
There are 23 citations in total.

Details

Subjects Engineering
Journal Section Articles
Authors

Emre Ceyhan This is me

Ayşe Mercangöz This is me

Nimet Karakoç This is me

Sevim Bilgiç This is me

Publication Date April 1, 2010
Published in Issue Year 2010 Volume: 7 Issue: 2

Cite

APA Ceyhan, E., Mercangöz, A., Karakoç, N., Bilgiç, S. (2010). İlaç Hammaddesi Olarak Sentezlenen Elektrofilik ve Nonelektrofilik Fenolik Schiff Bazlarının Umu Test Sistemi ile Genotoksik Aktivitesinin Araştırılması. Cankaya University Journal of Science and Engineering, 7(2).
AMA Ceyhan E, Mercangöz A, Karakoç N, Bilgiç S. İlaç Hammaddesi Olarak Sentezlenen Elektrofilik ve Nonelektrofilik Fenolik Schiff Bazlarının Umu Test Sistemi ile Genotoksik Aktivitesinin Araştırılması. CUJSE. April 2010;7(2).
Chicago Ceyhan, Emre, Ayşe Mercangöz, Nimet Karakoç, and Sevim Bilgiç. “İlaç Hammaddesi Olarak Sentezlenen Elektrofilik Ve Nonelektrofilik Fenolik Schiff Bazlarının Umu Test Sistemi Ile Genotoksik Aktivitesinin Araştırılması”. Cankaya University Journal of Science and Engineering 7, no. 2 (April 2010).
EndNote Ceyhan E, Mercangöz A, Karakoç N, Bilgiç S (April 1, 2010) İlaç Hammaddesi Olarak Sentezlenen Elektrofilik ve Nonelektrofilik Fenolik Schiff Bazlarının Umu Test Sistemi ile Genotoksik Aktivitesinin Araştırılması. Cankaya University Journal of Science and Engineering 7 2
IEEE E. Ceyhan, A. Mercangöz, N. Karakoç, and S. Bilgiç, “İlaç Hammaddesi Olarak Sentezlenen Elektrofilik ve Nonelektrofilik Fenolik Schiff Bazlarının Umu Test Sistemi ile Genotoksik Aktivitesinin Araştırılması”, CUJSE, vol. 7, no. 2, 2010.
ISNAD Ceyhan, Emre et al. “İlaç Hammaddesi Olarak Sentezlenen Elektrofilik Ve Nonelektrofilik Fenolik Schiff Bazlarının Umu Test Sistemi Ile Genotoksik Aktivitesinin Araştırılması”. Cankaya University Journal of Science and Engineering 7/2 (April 2010).
JAMA Ceyhan E, Mercangöz A, Karakoç N, Bilgiç S. İlaç Hammaddesi Olarak Sentezlenen Elektrofilik ve Nonelektrofilik Fenolik Schiff Bazlarının Umu Test Sistemi ile Genotoksik Aktivitesinin Araştırılması. CUJSE. 2010;7.
MLA Ceyhan, Emre et al. “İlaç Hammaddesi Olarak Sentezlenen Elektrofilik Ve Nonelektrofilik Fenolik Schiff Bazlarının Umu Test Sistemi Ile Genotoksik Aktivitesinin Araştırılması”. Cankaya University Journal of Science and Engineering, vol. 7, no. 2, 2010.
Vancouver Ceyhan E, Mercangöz A, Karakoç N, Bilgiç S. İlaç Hammaddesi Olarak Sentezlenen Elektrofilik ve Nonelektrofilik Fenolik Schiff Bazlarının Umu Test Sistemi ile Genotoksik Aktivitesinin Araştırılması. CUJSE. 2010;7(2).