Salicylhydroxamic Acid Inhibits the Growth of Candida albicans
Candida spp. are common and aggressive pathogens.
Because of the growing resistance of Candida spp. to current
antifungals, novel targets, found in Candida spp. but not in humans
or other flora, have to be identified. The alternative oxidase (AOX)
is one such possibility. This enzyme is insensitive to cyanide, but is
sensitive to compounds such as salicylhydroxamic acid (SHAM),
disulfiram and n-alkyl gallates. The growth Candida albicans was
inhibited by SHAM (Ki = 9-15 mM) and cyanide (Ki = 2-4 mM),
albeit to differing extents. The rate of O2 uptake was inhibited by
less than 10% by 25 mM SHAM and by about 90% by 250 μM
KCN. Although SHAM substantially inhibited the growth of C.
albicans, it is unlikely that the inhibition of AOX was the cause.
Salicylhydroxamic acid is used therapeutically in the treatment of
urinary tract infections and urolithiasis, but it also has some potential
in the treatment of C. albicans infection.
[1] A. M. Tortorano, J. Peman, H. Bernhardt, L. Klingspor, C. C. Kibbler,
O. Faure, E. Biraghi, E. Canton, K. Zimmermann, S. Seaton, and R.
Grillot, "Epidemiology of candidaemia in Europe: results of 28-month
European Confederation of Medical Mycology (ECMM) hospital-based
surveillance study," European Journal of Clinical Microbiology and
Infectious Diseases, vol. 23, pp. 317-322, 2004.
[2] M. A. Pfaller, R. N. Jones, G. V. Doern, H. S. Sader, S. A. Messer, A.
Houston, S. Coffman, and R. J. Hollis, "Bloodstream infections due to
Candida species: SENTRY Antimicrobial Surveillance Program in
North America and Latin America, 1997-1998," Antimicrobial Agents
and Chemotherapy, vol. 44, pp. 747-751, 2000.
[3] O. Gudlaugsson, S. Gillespie, K. Lee, J. Vande Berg, J. Hu, S. Messer,
L. Herwaldt, M. Pfaller, and D. Diekema, "Attributable mortality of
nosocomial candidemia, revisited," Clinical Infectious Diseases, vol. 37,
pp. 1172-1177, 2003.
[4] G. R. Schonbaum, W. D. Bonner, Jr., B. T. Storey, and J. T. Bahr,
"Specific inhibition of the cyanide-insensitive respiratory pathway in
plant mitochondria by hydroxamic acids," Plant Physiology, vol. 47, pp.
124-128, 1971.
[5] J. N. Siedow and M. E. Girvin, "Alternative Respiratory Pathway: Its
role in seed respiration and its inhibition by propyl gallate.," Plant
Physiology, vol. 65, pp. 669-674, 1980.
[6] J. N. Siedow and D. M. Bickett, "Structural features required for
inhibition of cyanide-insensitive electron transfer by propyl gallate,"
Archive of Biochemistry and Biophysics, vol. 207, pp. 32-39, 1981.
[7] L. Yan, M. Li, Y. Cao, P. Gao, Y. Cao, Y. Wang, and Y. Jiang, "The
alternative oxidase of Candida albicans causes reduced fluconazole
susceptibility," Journal of Antimicrobial Chemotherapy, vol. to be
published, 2009.
[8] N. Sen and H. K. Majumder, "Mitochondrion of protozoan parasite
emerges as potent therapeutic target: exciting drugs are on the horizon,"
Current Pharmaceutical Design, vol. 14, pp. 839-846, 2008.
[9] A. Veiga, J. D. Arrabaca, and M. C. Loueiro-Dias, "Stress situations
induce cyanide-resistant respiration in spoilage yeasts," Journal of
Applied Microbiology, vol. 95, pp. 364-371, 2003.
[10] V. N. Popov, R. A. Simonian, V. P. Skulachev, and A. A. Starkov,
"Inhibition of the alternative oxidase stimulates H2O2 production in plant
mitochondria," FEBS Letters, vol. 415, pp. 87-90, 1997.
[11] S.-Y. M. Pang, S. Tristram, and S. Brown, "An in silico model of the
alternative oxidase," International Journal of Biosciences and
Technology, vol. submitted for publication, 2009.
[12] R. M. Nervig and S. Kadis, "Effect of hydroxamic acids on growth and
urease activity in Corynebacterium renale," Canadian Journal of
Microbiology, vol. 22, pp. 544-551, 1976.
[13] C. Y. Wang and L. H. Lee, "Mutagenicity and antibacterial activity of
hydroxamic acids," Antimicrobial Agents and Chemotherapy, vol. 11,
pp. 753-755, 1977.
[14] J. J. Gavin, "Analytical microbiology. II. The diffusion methods,"
Applied Microbiology, vol. 5, pp. 25-33, 1957.
[15] S. Budavari, "The Merck Index," 12 ed. Whitehouse Station: Merck &
Co., Inc., 1996.
[16] A.-E. A. Salem and M. M. Omar, "Atomic absorption and
spectrophotometric determinations of salicylhydroxamix acid in its pure
and pharmeceutical dosage forms," Turkish Journal of Chemistry, vol.
27, pp. 383-393, 2003.
[17] B. Gompertz, "On the nature of the function expressive of the law of
human mortality, and on a new mode of determining the value of life
contingencies.," Philosophical Transactions of the Royal Society of
London, vol. 115, pp. 513-585, 1825.
[18] M. H. Zweitering, I. Jongenburger, F. M. Rombouts, and K. van't Riet,
"Modeling of the bacterial growth curve.," Applied and Environmental
Microbiology, vol. 56, pp. 1875-1881, 1990.
[19] R Development Core Team, "R: A language and environment for
statistical computing." Vienna, Austria: R Foundation for Statistical
Computing, 2006.
[20] R. K. Finn, "Theory of agar diffusion methods of assay.," Analytical
Chemistry, vol. 31, pp. 975-977, 1959.
[21] M. L. Delignette-Muller and J. P. Flandrois, "An accurate diffusion
method for determining bacterial sensitivity to antibiotics.," Journal of
Antimicrobial Chemothrapy, vol. 34, pp. 73-81, 1994.
[22] A. L. Koch, "Diffusion through agar blocks of finite dimensions: a
theoretical analysis of three systems of practical significance in
microbiology.," Microbiology, vol. 145, pp. 643-654, 1999.
[23] S. Brown and N. L. Taylor, "Inhibition of mitochondrial electron transfer
by antipsychotic medication," Human and Veterinary Toxicology, vol.
42, pp. 209-211, 2000.
[24] J. B. Hiskey and V. M. Sanchez, "Mechanistic and kinetic aspects of
silver dissolution in cyanide solutions.," Journal of Applied
Electrochemistry, vol. 20, pp. 479-487, 1990.
[25] B. K. Davis, "Diffusion in polymer gel implants.," Proceedings of the
National Academy of Sciences of the USA, vol. 71, pp. 3120-3123, 1974.
[26] L. Friedman, "Structure of agar gels from studies of diffusion.," Journal
of the American Chemical Society, vol. 52, pp. 1311-1314, 1930.
[27] N. Fatin-Rogue, K. Starchev, and J. Buffle, "Size effects on diffusion
processes within agarose gels.," Biophysical Journal, vol. 86, pp. 2710-
2719, 2004.
[28] E. J. Schantz and M. A. Lauffer, "Diffusion measurements in agar gel.,"
Biochemistry, vol. 1, pp. 658-663, 1962.
[29] W. G. Bardsley, P. Leff, J. Kavanagh, and R. D. Waight, "Deviations
from Michaelis-Menten kinetics. The possibility of complicated curves
for simple kinetic schemes and the computer fitting of experimental data
for acetylcholinesterase, acid phosphatase, adenosine deaminase,
arylsulphatase, benzylamine oxidase, chymotrypsin, fumarase, galactose
dehydrogenase, β-galactosidase, lactate dehydrogenase, peroxidase and
xanthine oxidase.," Biochemical Journal, vol. 187, pp. 739-765, 1980.
[30] R. Battino, T. R. Rettich, and T. Tominaga, "The solubility of oxygen
and ozone in liquids," Journal of Physical and Chemical Reference
Data, vol. 12, pp. 163-178, 1983.
[31] S. Aoki and S. Ito-Kuwa, "Respiration of Candida albicans in relation to
its morphogenesis," Plant and Cell Physiology, vol. 23, pp. 721-726,
1982.
[32] Nomenclature Committee of the International Union of Biochemistry,
"Symbolism and terminology in enzyme kinetics.," European Journal of
Biochemistry, vol. 128, pp. 281-291, 1982.
[33] O. Schabenberger, B. E. Tharp, J. J. Kells, and D. Penner, "Statistical
tests for hormesis and effective dosages in herbicide dose response.,"
Agronomy Journal, vol. 91, pp. 713-721, 1999.
[34] P. R. Rich, N. K. Wiegand, H. Blum, A. L. Moore, and W. D. Bonner,
Jr., "Studies on the mechanism of inhibition of redox enzymes by
substituted hydroxamic acids," Biochimica et Biophysica Acta, vol. 525,
pp. 325-337, 1978.
[35] J. Hase and K. Kobashi, "Inhibition of Proteus vulgaris urease by
hydroxamic acids.," Journal of Biochemistry, vol. 62, pp. 293-299, 1967.
[36] K. Kobashi, J. Hase, and K. Uehara, "Specific inhibition of urease by
hydroxamic acids," Biochimica et Biophysica Acta, vol. 65, pp. 380-383,
1962.
[37] W. N. Fishbein and P. P. Carbone, "Urease Catalysis. Ii. Inhibition of the
Enzyme by Hydroxyurea, Hydroxylamine, and Acetohydroxamic Acid,"
Journal of Biological Chemistry, vol. 240, pp. 2407-2414, 1965.
[38] B. Davies and D. W. Edwards, "Inhibition of myeloperoxidase by
salicylhydroxamic acid.," Biochemical Journal, vol. 258, pp. 801-806,
1989.
[39] T. Jones, N. A. Federspiel, H. Chibana, J. Dungan, S. Kalman, B. B.
Magee, G. Newport, Y. R. Thorstenson, N. Agabian, P. T. Magee, R. W.
Davis, and S. Scherer, "The diploid genome sequence of Candida
albicans," Proceedings of the National Academy of Sciences of the USA,
vol. 101, pp. 7329-7334, 2004.
[40] J. H. Bell and R. F. Pratt, "Mechanism of inhibition of the betalactamase
of Enterobacter cloacae P99 by 1:1 complexes of vanadate
with hydroxamic acids," Biochemistry, vol. 41, pp. 4329-4338, 2002.
[41] G. R. Gale, "Selective inhibition of deoxyribonucleic acid synthesis by
salicylhydroxamic acid.," Proceedings of the Society for Experimental
Biology and Medicine., vol. 122, pp. 1236-1240, 1966.
[42] I. Khozin-Goldberg, C. Bigogno, and Z. Cohen, "Salicylhydroxamic acid
inhibits D6 desaturation in the microalga Porphyridium cruentum.,"
Biochimica et Biophysica Acta, vol. 1439, pp. 384-394, 1999.
[43] D. Leung, G. Abbenante, and D. P. Fairlie, "Protease inhibitors: current
status and future prospects," Journal of Medicinal Chemistry, vol. 43,
pp. 305-341, 2000.
[44] J. B. Summers, K. H. Kim, H. Mazdiyasni, J. H. Holms, J. D. Ratajczyk,
A. O. Stewart, R. D. Dyer, and G. W. Carter, "Hydroxamic acid
inhibitors of 5-lipoxygenase: quantitative structure-activity
relationships," Journal of Medicinal Chemistry, vol. 33, pp. 992-998,
1990.
[45] E. C. O'Brien, S. Le Roy, J. Levaillain, D. J. Fitzgerald, and K. B. Nolan,
"Metal complexes of salicylhydroxamic acid and Oacetylsalicylhydroxamic
acid," Inorganica Chimica Acta, vol. 266, pp.
117-120, 1997.
[46] C. J. Marmion, D. Griffith, and K. B. Nolan, "Hydroxamic acids - an
intriguing family of enzyme inhibitors and biomedical ligands,"
European Journal of Inorganic Chemistry, vol. 2004, pp. 3003-3017,
2004.
[47] V. Špringer, M. Hornácková, R. Karlícek, and B. Kopecká,
"Salicylhydroxamic acids and its iron(III) complexes.," Collection of
Czechoslovak Chemical Communications, vol. 52, pp. 602-608, 1987.
[48] B. Coyle, K. Kavanagh, M. McCann, M. Devereux, and M. Geraghty,
"Mode of anti-fungal activity of 1,10-phenanthroline and its Cu(II),
Mn(II) and Ag(I) complexes," Biometals, vol. 16, pp. 321-329, 2003.
[49] P. R. Rich, A. L. Moore, and W. D. Bonner, Jr, "The effects of
bathophenanthroline, bathophenanthrolinesulphonate and 2-
thenoyltrifluoroacetone on mung-bean mitochondria and
submitochondrial particles," Biochemical Journal, vol. 162, pp. 205-208,
1977.
[50] H. J. Harmon and F. L. Crane, "Inhibition of mitochondrial electron
transport by hydrophilic metal chelators. Determination of
dehydrogenase topography," Biochimica et Biophysica Acta, vol. 440,
pp. 45-58, 1976.
[51] N. Schnell and K. D. Entian, "Identification and characterization of a
Saccharomyces cerevisiae gene (PAR1) conferring resistance to iron
chelators," European Journal of Biochemistry, vol. 200, pp. 487-493,
1991.
[1] A. M. Tortorano, J. Peman, H. Bernhardt, L. Klingspor, C. C. Kibbler,
O. Faure, E. Biraghi, E. Canton, K. Zimmermann, S. Seaton, and R.
Grillot, "Epidemiology of candidaemia in Europe: results of 28-month
European Confederation of Medical Mycology (ECMM) hospital-based
surveillance study," European Journal of Clinical Microbiology and
Infectious Diseases, vol. 23, pp. 317-322, 2004.
[2] M. A. Pfaller, R. N. Jones, G. V. Doern, H. S. Sader, S. A. Messer, A.
Houston, S. Coffman, and R. J. Hollis, "Bloodstream infections due to
Candida species: SENTRY Antimicrobial Surveillance Program in
North America and Latin America, 1997-1998," Antimicrobial Agents
and Chemotherapy, vol. 44, pp. 747-751, 2000.
[3] O. Gudlaugsson, S. Gillespie, K. Lee, J. Vande Berg, J. Hu, S. Messer,
L. Herwaldt, M. Pfaller, and D. Diekema, "Attributable mortality of
nosocomial candidemia, revisited," Clinical Infectious Diseases, vol. 37,
pp. 1172-1177, 2003.
[4] G. R. Schonbaum, W. D. Bonner, Jr., B. T. Storey, and J. T. Bahr,
"Specific inhibition of the cyanide-insensitive respiratory pathway in
plant mitochondria by hydroxamic acids," Plant Physiology, vol. 47, pp.
124-128, 1971.
[5] J. N. Siedow and M. E. Girvin, "Alternative Respiratory Pathway: Its
role in seed respiration and its inhibition by propyl gallate.," Plant
Physiology, vol. 65, pp. 669-674, 1980.
[6] J. N. Siedow and D. M. Bickett, "Structural features required for
inhibition of cyanide-insensitive electron transfer by propyl gallate,"
Archive of Biochemistry and Biophysics, vol. 207, pp. 32-39, 1981.
[7] L. Yan, M. Li, Y. Cao, P. Gao, Y. Cao, Y. Wang, and Y. Jiang, "The
alternative oxidase of Candida albicans causes reduced fluconazole
susceptibility," Journal of Antimicrobial Chemotherapy, vol. to be
published, 2009.
[8] N. Sen and H. K. Majumder, "Mitochondrion of protozoan parasite
emerges as potent therapeutic target: exciting drugs are on the horizon,"
Current Pharmaceutical Design, vol. 14, pp. 839-846, 2008.
[9] A. Veiga, J. D. Arrabaca, and M. C. Loueiro-Dias, "Stress situations
induce cyanide-resistant respiration in spoilage yeasts," Journal of
Applied Microbiology, vol. 95, pp. 364-371, 2003.
[10] V. N. Popov, R. A. Simonian, V. P. Skulachev, and A. A. Starkov,
"Inhibition of the alternative oxidase stimulates H2O2 production in plant
mitochondria," FEBS Letters, vol. 415, pp. 87-90, 1997.
[11] S.-Y. M. Pang, S. Tristram, and S. Brown, "An in silico model of the
alternative oxidase," International Journal of Biosciences and
Technology, vol. submitted for publication, 2009.
[12] R. M. Nervig and S. Kadis, "Effect of hydroxamic acids on growth and
urease activity in Corynebacterium renale," Canadian Journal of
Microbiology, vol. 22, pp. 544-551, 1976.
[13] C. Y. Wang and L. H. Lee, "Mutagenicity and antibacterial activity of
hydroxamic acids," Antimicrobial Agents and Chemotherapy, vol. 11,
pp. 753-755, 1977.
[14] J. J. Gavin, "Analytical microbiology. II. The diffusion methods,"
Applied Microbiology, vol. 5, pp. 25-33, 1957.
[15] S. Budavari, "The Merck Index," 12 ed. Whitehouse Station: Merck &
Co., Inc., 1996.
[16] A.-E. A. Salem and M. M. Omar, "Atomic absorption and
spectrophotometric determinations of salicylhydroxamix acid in its pure
and pharmeceutical dosage forms," Turkish Journal of Chemistry, vol.
27, pp. 383-393, 2003.
[17] B. Gompertz, "On the nature of the function expressive of the law of
human mortality, and on a new mode of determining the value of life
contingencies.," Philosophical Transactions of the Royal Society of
London, vol. 115, pp. 513-585, 1825.
[18] M. H. Zweitering, I. Jongenburger, F. M. Rombouts, and K. van't Riet,
"Modeling of the bacterial growth curve.," Applied and Environmental
Microbiology, vol. 56, pp. 1875-1881, 1990.
[19] R Development Core Team, "R: A language and environment for
statistical computing." Vienna, Austria: R Foundation for Statistical
Computing, 2006.
[20] R. K. Finn, "Theory of agar diffusion methods of assay.," Analytical
Chemistry, vol. 31, pp. 975-977, 1959.
[21] M. L. Delignette-Muller and J. P. Flandrois, "An accurate diffusion
method for determining bacterial sensitivity to antibiotics.," Journal of
Antimicrobial Chemothrapy, vol. 34, pp. 73-81, 1994.
[22] A. L. Koch, "Diffusion through agar blocks of finite dimensions: a
theoretical analysis of three systems of practical significance in
microbiology.," Microbiology, vol. 145, pp. 643-654, 1999.
[23] S. Brown and N. L. Taylor, "Inhibition of mitochondrial electron transfer
by antipsychotic medication," Human and Veterinary Toxicology, vol.
42, pp. 209-211, 2000.
[24] J. B. Hiskey and V. M. Sanchez, "Mechanistic and kinetic aspects of
silver dissolution in cyanide solutions.," Journal of Applied
Electrochemistry, vol. 20, pp. 479-487, 1990.
[25] B. K. Davis, "Diffusion in polymer gel implants.," Proceedings of the
National Academy of Sciences of the USA, vol. 71, pp. 3120-3123, 1974.
[26] L. Friedman, "Structure of agar gels from studies of diffusion.," Journal
of the American Chemical Society, vol. 52, pp. 1311-1314, 1930.
[27] N. Fatin-Rogue, K. Starchev, and J. Buffle, "Size effects on diffusion
processes within agarose gels.," Biophysical Journal, vol. 86, pp. 2710-
2719, 2004.
[28] E. J. Schantz and M. A. Lauffer, "Diffusion measurements in agar gel.,"
Biochemistry, vol. 1, pp. 658-663, 1962.
[29] W. G. Bardsley, P. Leff, J. Kavanagh, and R. D. Waight, "Deviations
from Michaelis-Menten kinetics. The possibility of complicated curves
for simple kinetic schemes and the computer fitting of experimental data
for acetylcholinesterase, acid phosphatase, adenosine deaminase,
arylsulphatase, benzylamine oxidase, chymotrypsin, fumarase, galactose
dehydrogenase, β-galactosidase, lactate dehydrogenase, peroxidase and
xanthine oxidase.," Biochemical Journal, vol. 187, pp. 739-765, 1980.
[30] R. Battino, T. R. Rettich, and T. Tominaga, "The solubility of oxygen
and ozone in liquids," Journal of Physical and Chemical Reference
Data, vol. 12, pp. 163-178, 1983.
[31] S. Aoki and S. Ito-Kuwa, "Respiration of Candida albicans in relation to
its morphogenesis," Plant and Cell Physiology, vol. 23, pp. 721-726,
1982.
[32] Nomenclature Committee of the International Union of Biochemistry,
"Symbolism and terminology in enzyme kinetics.," European Journal of
Biochemistry, vol. 128, pp. 281-291, 1982.
[33] O. Schabenberger, B. E. Tharp, J. J. Kells, and D. Penner, "Statistical
tests for hormesis and effective dosages in herbicide dose response.,"
Agronomy Journal, vol. 91, pp. 713-721, 1999.
[34] P. R. Rich, N. K. Wiegand, H. Blum, A. L. Moore, and W. D. Bonner,
Jr., "Studies on the mechanism of inhibition of redox enzymes by
substituted hydroxamic acids," Biochimica et Biophysica Acta, vol. 525,
pp. 325-337, 1978.
[35] J. Hase and K. Kobashi, "Inhibition of Proteus vulgaris urease by
hydroxamic acids.," Journal of Biochemistry, vol. 62, pp. 293-299, 1967.
[36] K. Kobashi, J. Hase, and K. Uehara, "Specific inhibition of urease by
hydroxamic acids," Biochimica et Biophysica Acta, vol. 65, pp. 380-383,
1962.
[37] W. N. Fishbein and P. P. Carbone, "Urease Catalysis. Ii. Inhibition of the
Enzyme by Hydroxyurea, Hydroxylamine, and Acetohydroxamic Acid,"
Journal of Biological Chemistry, vol. 240, pp. 2407-2414, 1965.
[38] B. Davies and D. W. Edwards, "Inhibition of myeloperoxidase by
salicylhydroxamic acid.," Biochemical Journal, vol. 258, pp. 801-806,
1989.
[39] T. Jones, N. A. Federspiel, H. Chibana, J. Dungan, S. Kalman, B. B.
Magee, G. Newport, Y. R. Thorstenson, N. Agabian, P. T. Magee, R. W.
Davis, and S. Scherer, "The diploid genome sequence of Candida
albicans," Proceedings of the National Academy of Sciences of the USA,
vol. 101, pp. 7329-7334, 2004.
[40] J. H. Bell and R. F. Pratt, "Mechanism of inhibition of the betalactamase
of Enterobacter cloacae P99 by 1:1 complexes of vanadate
with hydroxamic acids," Biochemistry, vol. 41, pp. 4329-4338, 2002.
[41] G. R. Gale, "Selective inhibition of deoxyribonucleic acid synthesis by
salicylhydroxamic acid.," Proceedings of the Society for Experimental
Biology and Medicine., vol. 122, pp. 1236-1240, 1966.
[42] I. Khozin-Goldberg, C. Bigogno, and Z. Cohen, "Salicylhydroxamic acid
inhibits D6 desaturation in the microalga Porphyridium cruentum.,"
Biochimica et Biophysica Acta, vol. 1439, pp. 384-394, 1999.
[43] D. Leung, G. Abbenante, and D. P. Fairlie, "Protease inhibitors: current
status and future prospects," Journal of Medicinal Chemistry, vol. 43,
pp. 305-341, 2000.
[44] J. B. Summers, K. H. Kim, H. Mazdiyasni, J. H. Holms, J. D. Ratajczyk,
A. O. Stewart, R. D. Dyer, and G. W. Carter, "Hydroxamic acid
inhibitors of 5-lipoxygenase: quantitative structure-activity
relationships," Journal of Medicinal Chemistry, vol. 33, pp. 992-998,
1990.
[45] E. C. O'Brien, S. Le Roy, J. Levaillain, D. J. Fitzgerald, and K. B. Nolan,
"Metal complexes of salicylhydroxamic acid and Oacetylsalicylhydroxamic
acid," Inorganica Chimica Acta, vol. 266, pp.
117-120, 1997.
[46] C. J. Marmion, D. Griffith, and K. B. Nolan, "Hydroxamic acids - an
intriguing family of enzyme inhibitors and biomedical ligands,"
European Journal of Inorganic Chemistry, vol. 2004, pp. 3003-3017,
2004.
[47] V. Špringer, M. Hornácková, R. Karlícek, and B. Kopecká,
"Salicylhydroxamic acids and its iron(III) complexes.," Collection of
Czechoslovak Chemical Communications, vol. 52, pp. 602-608, 1987.
[48] B. Coyle, K. Kavanagh, M. McCann, M. Devereux, and M. Geraghty,
"Mode of anti-fungal activity of 1,10-phenanthroline and its Cu(II),
Mn(II) and Ag(I) complexes," Biometals, vol. 16, pp. 321-329, 2003.
[49] P. R. Rich, A. L. Moore, and W. D. Bonner, Jr, "The effects of
bathophenanthroline, bathophenanthrolinesulphonate and 2-
thenoyltrifluoroacetone on mung-bean mitochondria and
submitochondrial particles," Biochemical Journal, vol. 162, pp. 205-208,
1977.
[50] H. J. Harmon and F. L. Crane, "Inhibition of mitochondrial electron
transport by hydrophilic metal chelators. Determination of
dehydrogenase topography," Biochimica et Biophysica Acta, vol. 440,
pp. 45-58, 1976.
[51] N. Schnell and K. D. Entian, "Identification and characterization of a
Saccharomyces cerevisiae gene (PAR1) conferring resistance to iron
chelators," European Journal of Biochemistry, vol. 200, pp. 487-493,
1991.
@article{"International Journal of Biological, Life and Agricultural Sciences:53818", author = "Shu-Ying Marissa Pang and Stephen Tristram and Simon Brown", title = "Salicylhydroxamic Acid Inhibits the Growth of Candida albicans", abstract = "Candida spp. are common and aggressive pathogens.
Because of the growing resistance of Candida spp. to current
antifungals, novel targets, found in Candida spp. but not in humans
or other flora, have to be identified. The alternative oxidase (AOX)
is one such possibility. This enzyme is insensitive to cyanide, but is
sensitive to compounds such as salicylhydroxamic acid (SHAM),
disulfiram and n-alkyl gallates. The growth Candida albicans was
inhibited by SHAM (Ki = 9-15 mM) and cyanide (Ki = 2-4 mM),
albeit to differing extents. The rate of O2 uptake was inhibited by
less than 10% by 25 mM SHAM and by about 90% by 250 μM
KCN. Although SHAM substantially inhibited the growth of C.
albicans, it is unlikely that the inhibition of AOX was the cause.
Salicylhydroxamic acid is used therapeutically in the treatment of
urinary tract infections and urolithiasis, but it also has some potential
in the treatment of C. albicans infection.", keywords = "alternative oxidase, Candida albicans, growth,respiration, salicylhydroxamic acid.", volume = "5", number = "4", pages = "210-7", }
