Synthesis and initial in vitro evaluations of novel antioxidant aroylhydrazone iron chelators with increased stability against plasma hydrolysis

Chemical Research in Toxicology

Volumn 24, Issue 3, 2011, Pages 290-302

  Hruskova, Katerina ^a   Kovarikova, Petra ^a   Bendova, Petra ^a   Haskova, Pavlina ^a   MacKova, Eliska ^a   Stariat, Jan ^a   Vavrova, Anna ^a   Vavrova, Katerina ^a   Simunek, Tomas ^a  

^a Charles University in Prague Faculty of Pharmacy   (Czech Republic)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIOXIDANT; N' [1 (2,4 DIHYDROXYPHENYL)ETHYLIDEN]ISONICOTINOYLHYDRAZIDE; N' [1 (2,6 DIHYDROXYPHENYL)ETHYLIDEN]ISONICOTINOYLHYDRAZIDE; N'(1 (7 HYDROXY 2 OXO 2H CHROMEN 8 YL)ETHYLIDENE)ISONICOTINOHYDRAZIDE; N'[1 (2 HYDROXY 4 METHOXYPHENYL)ETHYLIDEN]ISONICOTINOYLHYDRAZIDE; N'[1 (2 HYDROXY 5 NITROPHENYL)ETHYLIDEN]ISONICOTINOYLHYDRAZIDE; N'[1 (2 HYDROXYPHENYL)ETHYLIDEN]ISONICOTINOYLHYDRAZIDE; N'[1 (2 HYDROXYPHENYL)PROPYLIDEN]ISONICOTINOYLHYDRAZIDE; N'[1 (5 ACETYL 2,4 DIXYDROXYPHENYL)ETHYLIDEN]ISONICOTINOYLHYDRAZIDE; N'[1 (5 CHLORO 2 HYDROXYPHENYL)ETHYLIDEN]ISONICOTINOYLHYDRAZIDE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANTIOXIDANT ACTIVITY; ARTICLE; CELL PROTECTION; CHEMICAL BOND; CONTROLLED STUDY; DRUG STABILITY; DRUG STRUCTURE; DRUG SYNTHESIS; EVALUATION; EXPERIMENTAL RABBIT; HYDROLYSIS; IRON CHELATION; NONHUMAN; OXIDATIVE STRESS; PLASMA; RAT; SUBSTITUTION REACTION; TOXICITY TESTING;

ALDEHYDES; ANIMALS; ANTIOXIDANTS; CELL LINE; DRUG STABILITY; HYDRAZONES; HYDROLYSIS; HYDROXYL RADICAL; IRON CHELATING AGENTS; OXIDATIVE STRESS; RABBITS; RATS;

ORYCTOLAGUS CUNICULUS;

EID: 79952917106     PISSN: 0893228X     EISSN: 15205010     Source Type: Journal    
DOI: 10.1021/tx100359t     Document Type: Article

References (56)

1. Halliwell, B. and Gutteridge, J. M. C. (2007) Free Radicals in Biology and Medicine, 4 th ed., Oxford University Press, Oxford, U.K.
2. Griendling, K. K. and FitzGerald, G. A. (2003) Oxidative stress and cardiovascular injury: Part I: basic mechanisms and in vivo monitoring of ROS Circulation 108, 1912-1916 (Pubitemid 37296532)
3. Simunek, T., Sterba, M., Popelova, O., Adamcova, M., Hrdina, R., and Gersl, V. (2009) Anthracycline-induced cardiotoxicity: overview of studies examining the roles of oxidative stress and free cellular iron Pharmacol. Rep. 61, 154-171
4. Mladenka, P., Simunek, T., Hubl, M., and Hrdina, R. (2006) The role of reactive oxygen and nitrogen species in cellular iron metabolism Free Radical Res. 40, 263-272 (Pubitemid 43245441)
5. Reif, D. W. (1992) Ferritin as a source of iron for oxidative damage Free Radical Biol. Med. 12, 417-427
6. Kalinowski, D. S. and Richardson, D. R. (2005) The evolution of iron chelators for the treatment of iron overload disease and cancer Pharmacol. Rev. 57, 547-583 (Pubitemid 43036441)
7. Olivieri, N. F. and Brittenham, G. M. (1997) Iron-chelating therapy and the treatment of thalassemia Blood 89, 739-761 (Pubitemid 27121266)
8. Wood, J. C. (2008) Cardiac iron across different transfusion-dependent diseases Blood Rev. 22 (Suppl. 2) S14-S21
9. Galey, J. B. (2001) Recent advances in the design of iron chelators against oxidative damage Mini Rev. Med. Chem. 1, 233-242
10. Hasinoff, B. B., Hellmann, K., Herman, E. H., and Ferrans, V. J. (1998) Chemical, biological and clinical aspects of dexrazoxane and other bisdioxopiperazines Curr. Med. Chem. 5, 1-28 (Pubitemid 28083490)
11. Horackova, M., Ponka, P., and Byczko, Z. (2000) The antioxidant effects of a novel iron chelator salicylaldehyde isonicotinoyl hydrazone in the prevention of H(2)O(2) injury in adult cardiomyocytes Cardiovasc. Res. 47, 529-536 (Pubitemid 30646074)
12. Kurz, T., Gustafsson, B., and Brunk, U. T. (2006) Intralysosomal iron chelation protects against oxidative stress-induced cellular damage FEBS J. 273, 3106-3117
13. Lukinova, N., Iacovelli, J., Dentchev, T., Wolkow, N., Hunter, A., Amado, D., Ying, G. S., Sparrow, J. R., and Dunaief, J. L. (2009) Iron chelation protects the retinal pigment epithelial cell line ARPE-19 against cell death triggered by diverse stimuli Invest. Ophthalmol. Vis. Sci. 50, 1440-1447
14. Simunek, T., Boer, C., Bouwman, R. A., Vlasblom, R., Versteilen, A. M., Sterba, M., Gersl, V., Hrdina, R., Ponka, P., de Lange, J. J., Paulus, W. J., and Musters, R. J. (2005) SIH: a novel lipophilic iron chelator - protects H9c2 cardiomyoblasts from oxidative stress-induced mitochondrial injury and cell death J. Mol. Cell Cardiol. 39, 345-354 (Pubitemid 40995024)
15. Bendova, P., Mackova, E., Haskova, P., Vavrova, A., Jirkovsky, E., Sterba, M., Popelova, O., Kalinowski, D. S., Kovarikova, P., Vavrova, K., Richardson, D. R., and Simunek, T. (2010) Comparison of clinically used and experimental iron chelators for protection against oxidative stress-induced cellular injury Chem. Res. Toxicol. 23, 1105-1114
16. Simunek, T., Sterba, M., Popelova, O., Kaiserova, H., Adamcova, M., Hroch, M., Haskova, P., Ponka, P., and Gersl, V. (2008) Anthracycline toxicity to cardiomyocytes or cancer cells is differently affected by iron chelation with salicylaldehyde isonicotinoyl hydrazone Br. J. Pharmacol. 155, 138-148
17. Sterba, M., Popelova, O., Simunek, T., Mazurova, Y., Potacova, A., Adamcova, M., Guncova, I., Kaiserova, H., Palicka, V., Ponka, P., and Gersl, V. (2007) Iron chelation-afforded cardioprotection against chronic anthracycline cardiotoxicity: a study of salicylaldehyde isonicotinoyl hydrazone (SIH) Toxicology 235, 150-166 (Pubitemid 46734545)
18. Berndt, C., Kurz, T., Selenius, M., Fernandes, A. P., Edgren, M. R., and Brunk, U. T. (2010) Chelation of lysosomal iron protects against ionizing irradiation Biochem. J. 432, 295-301
19. Klimtova, I., Simunek, T., Mazurova, Y., Kaplanova, J., Sterba, M., Hrdina, R., Gersl, V., Adamcova, M., and Ponka, P. (2003) A study of potential toxic effects after repeated 10-week administration of a new iron chelator - salicylaldehyde isonicotinoyl hydrazone (SIH) to rabbits Acta Med. (Hradec Kralove, Czech Repub.) 46, 163-170
20. Yiakouvaki, A., Savovic, J., Al-Qenaei, A., Dowden, J., and Pourzand, C. (2006) Caged-iron chelators a novel approach towards protecting skin cells against UVA-induced necrotic cell death J. Invest. Dermatol. 126, 2287-2295 (Pubitemid 44413176)
21. Charkoudian, L. K., Dentchev, T., Lukinova, N., Wolkow, N., Dunaief, J. L., and Franz, K. J. (2008) Iron prochelator BSIH protects retinal pigment epithelial cells against cell death induced by hydrogen peroxide J. Inorg. Biochem. 102, 2130-2135
22. Charkoudian, L. K., Pham, D. M., and Franz, K. J. (2006) A pro-chelator triggered by hydrogen peroxide inhibits iron-promoted hydroxyl radical formation J. Am. Chem. Soc. 128, 12424-12425 (Pubitemid 44476626)
23. Kovarikova, P., Klimes, J., Sterba, M., Popelova, O., Mokry, M., Gersl, V., and Ponka, P. (2005) Development of high-performance liquid chromatographic determination of salicylaldehyde isonicotinoyl hydrazone in rabbit plasma and application of this method to an in vivo study J. Sep. Sci. 28, 1300-1306 (Pubitemid 41195339)
24. Buss, J. L. and Ponka, P. (2003) Hydrolysis of pyridoxal isonicotinoyl hydrazone and its analogs Biochim. Biophys. Acta 1619, 177-186 (Pubitemid 36078355)
25. Richardson, D., Vitolo, L. W., Baker, E., and Webb, J. (1989) Pyridoxal isonicotinoyl hydrazone and analogues. Study of their stability in acidic, neutral and basic aqueous solutions by ultraviolet-visible spectrophotometry BioMetals 2, 69-76
26. Kovarikova, P., Mokry, M., Klimes, J., and Vavrova, K. (2006) HPLC study on stability of pyridoxal isonicotinoyl hydrazone J. Pharm. Biomed. Anal. 40, 105-112 (Pubitemid 43061224)
27. Kovarikova, P., Mrkvickova, Z., and Klimes, J. (2008) Investigation of the stability of aromatic hydrazones in plasma and related biological material J. Pharm. Biomed. Anal. 47, 360-370
28. Simunek, T., Sterba, M., Popelova, O., Kaiserova, H., Potacova, A., Adamcova, M., Mazurova, Y., Ponka, P., and Gersl, V. (2008) Pyridoxal isonicotinoyl hydrazone (PIH) and its analogs as protectants against anthracycline-induced cardiotoxicity Hemoglobin 32, 207-215 (Pubitemid 351264517)
29. Edward, J. T., Gauthier, M., Chubb, F. L., and Ponka, P. (1988) Synthesis of new acylhydrazones as iron-chelating compounds J. Chem. Eng. Data 33, 538-540
30. Sacconi, L. (1953) Acylhydrazones of ortho-oxyaldehydes and ortho-aminoaldehydes and ketones as tridentate complexing agents J. Am. Chem. Soc. 75, 5434-5435
31. Kumar, S. and Kumar, D. (2008) Polystyrene-supported iodobenzene diacetate (PSIBD)-mediated synthesis of 1,2-diacylbenzenes from 2-hydroxyaryl aldehyde/ketone acylhydrazones Synth. Commun. 38, 3683-3699
32. FDA Guidance for Industry: Bioanalytical Method Validation, May 2001, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/ Guidances/UCM070107.pdf.
33. Kimes, B. W. and Brandt, B. L. (1976) Properties of a clonal muscle cell line from rat heart Exp. Cell Res. 98, 367-381
34. Esposito, B. P., Epsztejn, S., Breuer, W., and Cabantchik, Z. I. (2002) A review of fluorescence methods for assessing labile iron in cells and biological fluids Anal. Biochem. 304, 1-18 (Pubitemid 34492837)
35. Glickstein, H., El, R. B., Link, G., Breuer, W., Konijn, A. M., Hershko, C., Nick, H., and Cabantchik, Z. I. (2006) Action of chelators in iron-loaded cardiac cells: Accessibility to intracellular labile iron and functional consequences Blood 108, 3195-3203
36. Repetto, G., del Peso, A., and Zurita, J. L. (2008) Neutral red uptake assay for the estimation of cell viability/cytotoxicity Nat. Protoc. 3, 1125-1131
37. Wang, H. and Joseph, J. A. (1999) Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader Free Radical Biol. Med. 27, 612-616 (Pubitemid 29408648)
38. Lipinski, C. A., Lombardo, F., Dominy, B. W., and Feeney, P. J. (2001) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings Adv. Drug Delivery Rev. 46, 3-26 (Pubitemid 33653411)
39. Buss, J. L., Hermes-Lima, M., and Ponka, P. (2002) Pyridoxal isonicotinoyl hydrazone and its analogues Adv. Exp. Med. Biol. 509, 205-229
40. Ponka, P., Richardson, D., Baker, E., Schulman, H. M., and Edward, J. T. (1988) Effect of pyridoxal isonicotinoyl hydrazone and other hydrazones on iron release from macrophages, reticulocytes and hepatocytes Biochim. Biophys. Acta 967, 122-129
41. Richardson, D. R., Tran, E. H., and Ponka, P. (1995) The potential of iron chelators of the pyridoxal isonicotinoyl hydrazone class as effective antiproliferative agents Blood 86, 4295-4306
42. Sardao, V. A., Oliveira, P. J., Holy, J., Oliveira, C. R., and Wallace, K. B. (2007) Vital imaging of H9c2 myoblasts exposed to tert-butylhydroperoxide: characterization of morphological features of cell death BMC Cell Biol. 8, 11
43. Minotti, G. (1989) tert-butyl hydroperoxide-dependent microsomal release of iron and lipid peroxidation. I. Evidence for the reductive release of nonheme, nonferritin iron Arch. Biochem. Biophys. 273, 137-143 (Pubitemid 19197901)
44. Hershko, C., Link, G., Konijn, A. M., and Cabantchik, Z. I. (2005) Objectives and mechanism of iron chelation therapy Ann. N.Y. Acad. Sci. 1054, 124-135 (Pubitemid 43031017)
45. Lim, C. K., Kalinowski, D. S., and Richardson, D. R. (2008) Protection against hydrogen peroxide-mediated cytotoxicity in Friedreich's ataxia fibroblasts using novel iron chelators of the 2-pyridylcarboxaldehyde isonicotinoyl hydrazone class Mol. Pharmacol. 74, 225-235 (Pubitemid 351872173)
46. Buss, J. L. and Ponka, P. (2003) Hydrolysis of pyridoxal isonicotinoyl hydrazone and its analogs Biochim. Biophys. Acta 1619, 177-186 (Pubitemid 36078355)
47. Harnsberger, H. F., Cochran, E. L., and Szmant, H. H. (1955) The basicity of hydrazones J. Am. Chem. Soc. 77, 5048-5050
48. Cordes, E. H. and Jencks, W. P. (1963) Mechanism of hydrolysis of Schiff bases derived from aliphatic amines J. Am. Chem. Soc. 85, 2843.
49. Kale, A. A. and Torchilin, V. P. (2007) Design, synthesis, and characterization of pH-sensitive PEG-PE conjugates for stimuli-sensitive pharmaceutical nanocarriers: the effect of substitutes at the hydrazone linkage on the ph stability of PEG-PE conjugates Bioconjugate Chem. 18, 363-370 (Pubitemid 46493506)
50. Galati, G., Chan, T., Wu, B., and O'Brien, P. J. (1999) Glutathione-dependent generation of reactive oxygen species by the peroxidase-catalyzed redox cycling of flavonoids Chem. Res. Toxicol. 12, 521-525 (Pubitemid 29282923)
51. Han van De, W., Gian, C., Gerd, F., and Oleg, A. R. (1996) Estimation of Caco-2 cell permeability using calculated molecular descriptors Quant. Struct.-Act. Relat. 15, 480-490
52. Krarup, L. H., Christensen, I. T., Hovgaard, L., and Frokjaer, S. (1998) Predicting drug absorption from molecular surface properties based on molecular dynamics simulations Pharm. Res. 15, 972-978 (Pubitemid 28356909)
53. Palm, K., Stenberg, P., Luthman, K., and Artursson, P. (1997) Polar molecular surface properties predict the intestinal absorption of drugs in humans Pharm. Res. 14, 568-571 (Pubitemid 27220272)
54. Mrkvickova, Z., Kovarikova, P., Klimes, J., Kalinowski, D., and Richardson, D. R. (2007) Development and validation of HPLC-DAD methods for the analysis of two novel iron chelators with potent anti-cancer activity J. Pharm. Biomed. Anal. 43, 1343-1351 (Pubitemid 46282386)
55. Stariat, J., Kovarikova, P., Klimes, J., Lovejoy, D. B., Kalinowski, D. S., and Richardson, D. R. (2009) HPLC methods for determination of two novel thiosemicarbazone anti-cancer drugs (N4mT and Dp44mT) in plasma and their application to in vitro plasma stability of these agents J. Chromatogr., B 877, 316-322
56. Buss, J. L., Neuzil, J., and Ponka, P. (2004) Oxidative stress mediates toxicity of pyridoxal isonicotinoyl hydrazone analogs Arch. Biochem. Biophys. 421, 1-9 (Pubitemid 37543490)