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Chemistry of antimony-based drugs in biological systems and studies of their mechanism of action

  • Frédéric Frézard , Cynthia Demicheli EMAIL logo , Kelly C. Kato , Priscila G. Reis and Edgar H. Lizarazo-Jaimes
Published/Copyright: February 21, 2013

Abstract

Antimonial drugs have been used for a century in the therapy of the parasitic disease leishmaniasis. Even though pentavalent antimonials are still first-line drugs, they exhibit several limitations, including severe side effects, the need for daily parenteral administration and drug resistance. The molecular structure of pentavalent antimonials, their metabolism and mechanism of action, are still being investigated. Previous studies suggest that pentavalent antimony acts as a prodrug which is converted to the active and more toxic trivalent antimony. Other works support the direct involvement of pentavalent antimony. Recent data indicate that thiols and ribose-containing biomolecules may mediate the pharmacological action of these drugs. Trypanothione reductase and zinc-finger proteins were identified as possible molecular targets. This review summarizes the progress achieved to date on the chemistry of antimonial drugs in biological systems.


Corresponding author: Cynthia Demicheli, Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Pampulha, 31270-901 Belo Horizonte, Minas Gerais, Brazil

This work was supported by grants from the Brazilian agencies, FAPEMIG, CAPES, CNPq and MCTI.

References

Adaui, V.; Castillo, D.; Zimic, M.; Gutierrez, A.; Decuypere, S.; Vanaerschot, M.; De Doncker, S.; Schnorbusch, K.; Maes, I.; Van der Auwera, G.; Maes, L.; Llanos-Cuentas, A.; Arevalo, J.; Dujardin, J. C. Comparative gene expression analysis throughout the life cycle of Leishmania braziliensis: diversity of expression profiles among clinical isolates. PLoS Negl. Trop. Dis.2011, 5, e1021.Search in Google Scholar

Allan, J. W. Persian Metal Technology 700-1300 A.D., Ithaca Press: London, U.K., 1979.Search in Google Scholar

Atayde, V.D.; Tschudi, C.; Ullu, E. The emerging world of small silencing RNAs in protozoan. Parasites. Trends Parasitol. 2011, 27, 321–327.Search in Google Scholar

Baes, C. F.; Mesmer, R. E. The Hydrolysis of Cations. Ed. John Wiley & Sons: New York, 1976.Search in Google Scholar

Bailar, J. C.; Emeleus, H. J.; Nyholm, R.; Trotman-Dickenson, A. F. Comprehensive Inorganic Chemistry. Ed. Pergamon Press: New York, 1973.Search in Google Scholar

Baiocco, P.; Colotti, G.; Franceschini, S.; Ilari, A. Molecular basis of antimony treatment in leishmaniasis. J. Med. Chem.2009, 52, 2603–2612.Search in Google Scholar

Basu, J. M.; Mookerjee, A.; Sen, P.; Bhaumik, S.; Sen, P.; Banerjee, S.; Naskar, K.; Choudhuri, S. K.; Saha, B.; Raha, S.; Roy, S. Sodium antimony gluconate induces generation of reactive oxygen species and nitric oxide via phosphoinositide 3-kinase and mitogen-activated protein kinase activation in Leishmania donovani-infected macrophages. Antimicrob. Agents Chemother. 2006, 50, 1788–1797.Search in Google Scholar

Basu, J. M.; Mookerjee, A.; Banerjee, R.; Saha, M.; Singh, S.; Naskar, K.; Tripathy, G.; Sinha, P.; Pandey, K.; Sundar, S.; Bimal, S.; Das, P. K.; Choudhuri, S. K.; Roy, S. Inhibition of ABC transporters abolishes antimony resistance in Leishmania infection. Antimicrob. Agents Chemother.2008, 52, 1080–1093.Search in Google Scholar

Berman, J. D. Human leishmaniasis: clinical, diagnostic, and chemotherapeutic developments in the last 10 years. Clin. Infect. Dis.1997, 24, 684–703.Search in Google Scholar

Berman, J. D.; Grogl, M. Leishmania mexicana: chemistry and biochemistry of sodium stibogluconate (Pentostam). Exp. Parasitol.1988, 67, 96–103.Search in Google Scholar

Berman, J. D.; Waddell, D.; Hanson, B. D. Biochemical mechanisms of the antileishmanial activity of sodium stibogluconate. Antimicrob. Agents Chemother. 1985, 27, 916–920.Search in Google Scholar

Berman, J. D.; Gallalee, J. V.; Best, J. M. Sodium stibogluconate (Pentostam) inhibition of glucose catabolism via the glycolytic pathway, and fatty acid beta-oxidation in Leishmania mexicana amastigotes. Biochem. Pharmacol. 1987, 36, 197–201.Search in Google Scholar

Bhandari, D.; Guha, K.; Bhaduri, N.; Saha, P. Ubiquitination of mRNA cycling sequence binding protein from Leishmania donovani (LdCSBP) modulates the RNA endonuclease activity of its Smr domain. FEBS Lett. 2011, 585, 809–813.Search in Google Scholar

Biyani, N.; Singh, A. K.; Mandal, S.; Chawla, B.; Madhubala, R. Differential expression of proteins in antimony-susceptible and -resistant isolates of Leishmania donovani. Mol. Biochem. Parasitol.2011, 179, 91–99.Search in Google Scholar

Brochu, C.; Wang, J.; Roy, G.; Messier, N.; Wang, X. Y.; Saravia, N. G.; Ouellette, M. Antimony uptake systems in the protozoan parasite Leishmania and accumulation differences in antimony-resistant parasites. Antimicrob Agents Chemother. 2003, 47, 3073–3079.Search in Google Scholar

Burguera, J. L.; Burguera, M.; Petit de Pena, Y.; Lugo, A.; Anez, N. Selective determination of antimony(III) and antimony(V) in serum and urine and of total antimony in skin biopsies of patients with cutaneous leishmaniasis treated with meglumine antimoniate. Trace Elem. Med.1993, 10, 66–70.Search in Google Scholar

Callahan, H. L.; Beverley, S. M. Heavy metal resistance: a new role for P- glycoproteins in Leishmania. J. Biol. Chem.1991, 266, 18427–18430.Search in Google Scholar

Chai, Y.; Yan, S.; Wong, I. L. K.; Chow, L. M. C.; Sun, H. Complexation of antimony [Sb(V)] with guanosine 5′-monophosphate and guanosine 5’-diphospho-D-mannose: formation of both mono and bis-adducts. J. Inorg. Biochem.2005, 99, 2257–2263.Search in Google Scholar

Chakraborty, A. K.; Majumder, H. K. Mode of action of pentavalent antimonials: specific inhibition of type I DNA topoisomerase of Leishmania donovani. Biochem. Biophys. Res. Commun.1988, 152, 605–611.Search in Google Scholar

Clayton, C.; Shapira, M. Post-transcriptional regulation of gene expression in trypanosomes and leishmanias. Mol. Biochem. Parasitol. 2007, 156, 93–101.Search in Google Scholar

Coelho, A. C.; Beverley, S. M.; Cotrim, P. C. Functional genetic identification of PRP1, an ABC transporter superfamily member conferring pentamidine resistance in Leishmania major. Mol. Biochem. Parasitol. 2003, 130, 83–90.Search in Google Scholar

Cole, A. C. E. Kala-azar in east Africa. Trans. R. Soc. Trop. Med. Hyg.1944, 37, 409–435.Search in Google Scholar

Cook, C. Leonard Rogers KCSI FRCP FRS (1868–1962) and the founding of the Calcutta School of Tropical Medicine. Notes Rec. R. Soc. 2006, 60, 171–181.Search in Google Scholar

Cunningham, M. L.; Fairlamb, A. H. Trypanothione reductase from Leishmania donovani. Purification, characterisation and inhibition by trivalent antimonials. Eur. J. Biochem. 1995, 230, 460–468.Search in Google Scholar

Demicheli, C. Synthesis of pentavalent antimony derivatives used in the treatment of protozoonoses. 1999. BR patent 9907575-0.Search in Google Scholar

Demicheli, C.; Frézard, F. New process for preparing derivaties of antimony. 2001. Brazil Patent Pending PI 0106305-7.Search in Google Scholar

Demicheli, C.; Frézard, F.; Lecouvey, M.; Garnier-Suillerot, A. Antimony(V) complex formation with adenine nucleosides in aqueous solution. Biochim. Biophys. Acta.2002, 1570, 192–198.Search in Google Scholar

Demicheli, C.; Ochoa, R.; Lula, I. S.; Gozzo, F. C.; Eberlin, M.; Frézard, F. Pentavalent organoantimonial derivatives: two simple and efficient synthetic methods for meglumine antimonate. Applied Organomet. Chem. 2003, 17, 226–231.Search in Google Scholar

Demicheli, C.; Santos, L. S.; Ferreira, C. S.; Bouchemal, N.; Hantz, E.; Eberlin, M. N.; Frézard, F. Synthesis and characterization of Sb(V)–adenosine and Sb(V)–guanosine complexes in aqueous solution. Inorg. Chim. Acta2006, 359, 159–167.Search in Google Scholar

Demicheli, C.; Frézard, F.; Mangrum, J. B.; Farrell, N. P. Interaction of trivalent antimony with a CCHC zinc finger domain: potential relevance to the mechanism of action of antimonial drugs. Chem. Commun.2008, 39, 4828–4830.Search in Google Scholar

Denton, H.; McGregor, J. C.; Coombs, G. H. Reduction of anti-leishmanial pentavalent antimonial drugs by a parasite-specific thiol-dependent reductase, TDR1. Biochem. J.2004, 381, 405–412.Search in Google Scholar

Deps, P. D.; Viana, M. C.; Falqueto, A.; Dietze, R. Comparative evaluation of efficacy and toxicity of antimoniate N-methylglucamine and sodium stibogluconate BP88 for the treatment of localized cutaneous leishmaniasis. Rev. Soc. Bras. Med. Trop. 2000, 33, 535–543.Search in Google Scholar

Di Cristina, G.; Caronia, G. Therapy of visceral leishmaniasis. Pathologica. 1915, 7, 82–83.Search in Google Scholar

Duffin, J.; René, P. Anti-moine; Anti-biotique. The public fortunes of the secret properties of antimony potassium tartrate (tartar emetic). J. Hist. Med. Allied Sci.1991, 46, 440–456.Search in Google Scholar

Dzamitika, S. A.; Falcão, C. A.; Oliveira, F. B.; Marbeuf, C.; Garnier-Suillerot, A.; Demicheli, C.; Rossi-Bergmann, B.; Frézard, F. Role of residual Sb(III) in meglumine antimoniate cytotoxicity and MRP1-mediated resistance. Chem. Biol. Int.2006, 160, 217–224.Search in Google Scholar

Estes, J. W. The Medical Skills of Ancient Egypt; Science History Publications: Canton, MA, 1989.Search in Google Scholar

Fairlamb, A. H.; Cerami, A. Metabolism and functions of trypanothione in the Kinetoplastida. Annu. Rev. Microbiol. 1992, 46, 695–729.Search in Google Scholar

Ferreira, C. S.; Martins, P. S.; Demicheli, C.; Brochu, C.; Ouellette, M.; Frézard, F. Thiol-induced reduction of antimony(V) into antimony(III): a comparative study with trypanothione, cysteinyl-glycine, cysteine and glutathione. BioMetals2003, 16, 441–443.Search in Google Scholar

Ferreira, C. S.; Pimenta, A. M. C.; Demicheli, C.; Frézard, F. Characterization of reactions of antimoniate and meglumine antimoniate with a guanine ribonucleoside at different pH. Biometals2006, 19, 573–581.Search in Google Scholar

Ferreira, C. S.; da Rocha, I. C. M.; Neto, R. L. M.; Melo, M. N.; Frézard, F.; Demicheli, C. Influence of the nucleobase on the physicochemical characteristics and biological activities of sbv-ribonucleoside complexes J. Braz. Chem. Soc.2010, 21, 1258–1265.Search in Google Scholar

Filella, M.; May, P. M. Computer simulation of the low-molecular-weight inorganic species distribution of antimony(III) and antimony(V) in natural waters. Geochim. Cosmochim. Acta2003, 67, 4013–4031.10.1016/S0016-7037(03)00095-4Search in Google Scholar

Franco, M. A.; Barbosa, A. C.; Rath, S.; Dorea, J. G. Antimony oxidation-states in antileishmanial drugs. Am. J. Trop. Med. Hyg.1995, 52, 435–437.Search in Google Scholar

Frézard, F.; Demicheli, C.; Ferreira, C. S.; Costa, M. A. P. Glutathione-induced conversion of pentavalent antimony to trivalent antimony in meglumine antimoniate. Antimicrob. Agents Chemother.2001, 45, 913–916.Search in Google Scholar

Frézard, F.; Martins, P. S.; Barbosa, M. C. M.; Pimenta, A. M. C.; Ferreira, W. A.; de Melo, J. E.; Mangrum, J. B.; Demicheli, C. New insights into the chemical structure and composition of the pentavalent antimonial drugs, meglumine antimonate and sodium stibogluconate. J. Inorg. Biochem.2008, 102, 656–665.Search in Google Scholar

Frézard, F.; Silva, H.; Pimenta, A. M. C.; Farrell, N.; Demicheli, C. Greater binding affinity of trivalent antimony to a CCCH zinc finger domain compared to CCHC domain of kinetoplastid proteins. Metallomics2012, 4, 433–440.Search in Google Scholar

Fyfe, P. K.; Westrop, G. D.; Silva, A. M.; Coombs, G. H.; Hunter, W. N. Leishmania TDR1 structure, a unique trimeric glutathione transferase capable of deglutathionylation and antimonial prodrug activation. Proc. Natl. Acad. Sci. USA2012, 109, 11693–11698.Search in Google Scholar

Gailliot, P. L. Process of preparation of antimony derivatives. Society of the chemical industries of Rhone-Poulenc. 1941.FR Patent 8.687.47.Search in Google Scholar

Gainey, D.; Short, S.; McCoy, K. L. Intracellular location of cysteine transport activity correlates with productive processing of antigen disulfide. J. Cell Physiol.1996, 168, 248–254.Search in Google Scholar

Goodwin, L. C.; Page, J. E. A study of the excretion of organic antimonials using a polarographic procedure. Biochem. J.1943, 22, 236–240.Search in Google Scholar

Gourbal, B.; Sonuc, N.; Bhattacharjee, H.; Legare, D.; Sundar, S.; Ouellette, M.; Rosen, B. P.; Mukhopadhyay, R. Drug uptake and modulation of drug resistance in Leishmania by an aquaglyceroporin. J. Biol. Chem.2004, 279, 31010–31017.Search in Google Scholar

Guerin, P. J.; Olliaro, P.; Sundar, S.; Boelaert, M.; Croft, S. L.; Desjeux, P.; Wasunna, M. K.; Bryceson, A. D. Visceral leishmaniasis: current status of control, diagnosis, and treatment, and a proposed research and development agenda. Lancet Infect. Dis. 2002, 2, 494–501.Search in Google Scholar

Hansen, H. R.; Pergantis, S. A. Mass spectrometric identification and characterization of antimony complexes with ribose-containing biomolecules and an RNA oligomer. Anal. Bioanal. Chem.2006, 385, 821–833.Search in Google Scholar

Hansen, H. R.; Hansen, C.; Jensen, K. P.; Hansen, S. H.; Sturup, S.; Gammelgaard, B. Characterization of sodium stibogluconate by online liquid separation cell technology monitored by ICPMS and ESMS and computational chemistry. Anal. Chem.2008, 80, 5993–6000.Search in Google Scholar

Hansen, C.; Hansen, E. W.; Hansen, H. R.; Gammelgaard, B.; Stürup, S. Reduction of Sb(V) in a human macrophage cell line measured by HPLC-ICP-MS. Biol. Trace Elem. Res.2011, 144, 234–243.Search in Google Scholar

Headley, J. V.; Yong, M. S.; Brooks, P. W.; Phillips, A. Fast-atom bombardment mass spectrometry of the organometallic parasiticide, meglumine antimonite. Rapid Comm. Mass Spectrom.1995, 9, 372–376.Search in Google Scholar

Jander, G.; Ostmann, H.-J. 1962. Antimony(V) solutions. II. electrochemical titration. Z. Anorg. Allg. Chem.1962, 315, 250–258.Search in Google Scholar

Joan, F. B.; Concepcio, M. C. New procedure for the preparation of antimonic acid derivatives applicable in the treatment of canine leishmaniosis. 1994.ES Patent 2.050.614.Search in Google Scholar

Krauth-Siegel, R. L.; Comini, M. A. Redox control in trypanosomatids, parasitic protozoa with trypanothione-based thiol metabolism. Biochim. Biophys. Acta2008, 1780, 1236–1248.Search in Google Scholar

Lai, W. S., Kennington, E. A., Blackshear, P. J. Interactions of CCCH zinc finger proteins with mRNA: non-binding tristetraprolin mutants exert an inhibitory effect on degradation of AU-rich element-containing mRNAs. J. Biol. Chem.2002,277, 9606–9613.Search in Google Scholar

Lefebvre, J.; Maria, H. Study of equilibria in fresh solutions of polyantimoniates. C. R. Acad. Sci. Paris1963, 256, 3121–3124.Search in Google Scholar

Légaré, D.; Richard, D.; Mukhopadhyay, R.; Stierhof, Y. D.; Rosen, B. P.; Haimeur, A.; Papadopoulou, B.; Ouellette, M. The Leishmania ATP-binding cassette protein PGPA is an intracellular metal-thiol transporter ATPase. J. Biol. Chem.2001, 276, 26301–26307.Search in Google Scholar

Leon, O.; Roth, M. Zinc fingers: DNA binding and protein-protein interactions. Biol. Res.2000, 33, 21–30.Search in Google Scholar

Lucumi, A.; Robledo, S.; Gama, V.; Saravia, N. G. Sensitivity of Leishmania Viannia panamensis to pentavalent antimony is correlated with the formation of cleavable DNA-protein complexes. Antimicrob. Agents Chemother.1998, 42, 1990–1995.Search in Google Scholar

Lukaszczyk, L.; Zyrnicki, W. Speciation analysis of Sb(III) and Sb(V) in antileishmaniotic drug using Dowex 1×4 resin from hydrochloric acid solution. J. Pharm. Biomed. Anal.2010, 52, 747–751.Search in Google Scholar

Marques-da-Silva, E. A.; De Oliveira, J. C.; Figueiredo, A. B.; Júnior, D. S. L; Carneiro, C. M.; Fietto, J. L. R.; Afonso, L. C. C. Extracellular nucleotide metabolism in Leishmania: influence of adenosine in the establishment of infection. Microbes Infect.2008, 10, 850–857.Search in Google Scholar

Marr, J. Purine analogs as chemotherapeutic agents in leishmaniasis and American trypanosomiasis. J. Lab. Clin. Med.1995, 118, 111–119.Search in Google Scholar

Marsden, P. D. Pentavalent antimonials: old drugs for new diseases. Rev. Soc. Bras. Med. Trop.1985, 18, 187–198.Search in Google Scholar

Mego, J. L. Stimulation of intralysosomal proteolysis by cysteinyl-glycine, a product of the action of gamma-glutamyl transpeptidase on glutathione. Biochim. Biophys. Acta1985, 841, 139–144.10.1016/0304-4165(85)90014-5Search in Google Scholar

Monte-Neto, R. L.; Coelho, A. C.; Raymond, F.; Légaré, D.; Corbeil, J.; Melo, M. N.; Frézard, F.; Ouellette, M. Gene expression profiling and molecular characterization of antimony resistance in Leishmania amazonensis. PLoS Negl. Trop. Dis.2011, 5, e1167.Search in Google Scholar

Morais-Teixeira, E.; De Carvalho, A. S.; Da Costa, J. C. S.; Duarte, S. L.; Mendonça, J. S.; Boechat, N.; Rabello, A. In vitro and in vivo activity of meglumine antimoniate produced at Farmanguinhos-Fiocruz, Brazil, against Leishmania (Leishmania) amazonensis, L (L.) chagasi and L (Viannia) braziliensis. Mem. Inst. Oswaldo Cruz2008, 10, 358–362.Search in Google Scholar

Mukherjee, S. B.; Das, M.; Sudhandiran, G.; Shaha, C. Increase in cytosolic Ca2+ levels through the activation of non-selective cation channels induced by oxidative stress causes mitochondrial depolarization leading to apoptosis-like death in Leishmania donovani promastigotes. J. Biol. Chem.2002, 277, 24717–24727.Search in Google Scholar

Mukhopadhyay, R.; Dey, S.; Xu, N.; Gage, D.; Lightbody, J.; Ouellette, M.; Rosen, B. P. Trypanothione overproduction and resistance to antimonials and arsenicals in Leishmania. Proc. Natl. Acad. Sci. USA1996, 93, 10383–10387.Search in Google Scholar

Muniz-Junqueira, M. I.; Paula-Coelho, V. N. Meglumine antimonate directly increases phagocytosis, superoxide anion and TNF-α production, but only via TNF-α it indirectly increases nitric oxide production by phagocytes of healthy individuals, in vitro. Int. Immunopharmacol.2008,8, 1633–1638.Search in Google Scholar

Murray, H. W. Clinical and experimental advances in treatment of visceral leishmaniasis. Antimicrob. Agents Chemother.2001, 45, 2185–2197.Search in Google Scholar

Nakano, H.; Ozawa, Y.; Yagasaki, A. Synthesis and characterization of the first polyantimonate, [Sb8O12(OH)20]4-J. Am. Chem. Soc. 1995, 117, 12007–12008.Search in Google Scholar

Oliveira, F. B.; Schettini, D. A.; Ferreira, C. S.; Rates, B.; Rocha, O. G. F.; Frézard, F.; Demicheli, C. Kinetics of antimony(V) reduction by L-cysteine. Pharmacological implications and application to the determination of antimony in pentavalent antimonial drugs J. Braz. Chem. Soc. 2006, 17, 1642–1650.Search in Google Scholar

Ouellette, M.; Fowler, F.; Borst, P. The amplified H circle of methotrexate resistant Leishmania tarentoleae contains a novel P-glycoprotein gene. EMBO J. 1990, 9, 1027–1033.Search in Google Scholar

Ouellette, M.; Drummelsmith, J.; Papadopoulou, B. Leishmaniasis: drugs in the clinic, resistance and new developments. Drug Resist. Updat.2004,7, 257–266.Search in Google Scholar

Papadopoulou, B.; Roy, G.; Dey, S.; Rosen, B. P.; Ouellette, M. Contribution of the Leishmania P-glycoprotein-related gene ltpgpA to oxyanion resistance. J. Biol. Chem.1994, 22, 269, 11980–11986.Search in Google Scholar

Pathak, M. K.; Yi, T. Sodium stibogluconate is a potent inhibitor of protein tyrosine phosphatases and augments cytokine responses in hemopoietic cell lines. J. Immunol.2001, 167, 3391–3397.Search in Google Scholar

Perry, M. R.; Wyllie, S.; Prajapati, V. K.; Feldmann, J.; Sundar, S.; Boelaert, M.; Fairlamb, A. H. Visceral leishmaniasis and arsenic: an ancient poison contributing to antimonial treatment failure in the Indian subcontinent?. PloS Negl. Trop. Dis.2011, 5, e1227.Search in Google Scholar

Pitman, A. L.; Pourbaix, M.; de Zoubov, N. Potential-pH diagram of the antimony-water system. Its applications to properties of the metal, its compounds, its corrosion, and antimony electrodes. J. Electrochem. Soc.1957, 104, 594–600.Search in Google Scholar

Plimmer, H. G.; Thomson, J. D. Further results of the experimental treatment of trypanosomiasis in rats; being a progress report of a committee of the Royal Society. Proc. R. Soc. Lond. B.1908, 80, 1–10.Search in Google Scholar

Roberts, W. L.; Rainey, P. M. Antileishmanial activity of sodium stibogluconate fractions, Antimicrob. Agents Chemother.1993, 37, 1842–1846.Search in Google Scholar

Roberts, W. L.; Berman, J. D.; Rainey, P. M. In vitro antileishmanial properties of tri- and pentavalent antimonial preparations. Antimicrob. Agents Chemother.1995, 39, 1234–1239.Search in Google Scholar

Roberts, W. L.; McMurray, W. J.; Rainey, P. M. Characterization of the antimonial antileishmanial agent meglumine antimonate (Glucantime). Antimicrob. Agents Chemother.1998, 42, 1076–1082.Search in Google Scholar

Rogers, M. B.; Hilley, J. D.; Dickens, N. J.; Wilkes, J.; Bates, P. A.; Depledge, D. P.; Harris, D.; Her, Y.; Herzyk, P.; Imamura, H.; Otto, T. D.; Sanders, M.; Seeger, K.; Dujardin J.-C.; Berriman, M.; Smith, D. F.; Hertz-Fowler, C.; Mottram, J. C. Chromosome and gene copy number variation allow major structural change between species and strains of Leishmania. Genome Res.2011, 21, 2129–2142.Search in Google Scholar

Sansom, F. M., Robson, S. C., Hartland, E. L. Possible effects of microbial ecto-nucleoside triphosphate diphosphohydrolases on host-pathogen interactions. Microbiol. Mol. Biol. Rev.2008, 72, 765–768.Search in Google Scholar

Santos, R. F., Possa, M. A., Bastos, M. S., Guedes, P. M., Almeida, M. R., Demarco, R., Verjovski-Almeida, S., Bahia, M. T., Fietto, J. L. Influence of Ecto-nucleoside triphosphate diphosphohydrolase activity on Trypanosoma cruzi infectivity and virulence. PLOS Negl. Trop. Dis.2009, 3, e387, 1–9.Search in Google Scholar

Savage-Smith, E. Dioscorides on Pharmacy and Medicine. Ed. In J. M. Riddle, University of Texas Press: Austin, 1985, pp. 96–97.Search in Google Scholar

Sereno, D.; Holzmuller, P.; Mangot, I.; Cuny, G.; Ouaissi, A.; Lemesre, J. Antimonial-mediated DNA fragmentation in Leishmania infantum amastigotes Antimicrob. Agents Chemother.2001, 45, 2064–2069.Search in Google Scholar

Shaked-Mishan, P.; Ulrich, N.; Ephros, M.; Zilberstein, D. Novel intracellular Sb(V) reducing activity correlates with antimony susceptibility in Leishmania donovani. J. Biol. Chem.2001, 276, 3971–3976.Search in Google Scholar

Steck, E. A. The leishmaniases. Prog. Drug Res.1974,18, 289–351.Search in Google Scholar

Sterkers, Y.; Lachaud, L.; Bourgeois, N.; Crobu, L.; Bastien, P.; Pagès, M. Novel insights into genome plasticity in Eukaryotes: mosaic aneuploidy in Leishmania. Mol. Microbiol.2012, 86, 15–23.Search in Google Scholar

Sudhandiran, G.; Shaha, C. Antimonial induced increase in intracellular Ca2+ through non-selective cation channels in the host and the parasite is responsible for apoptosis of intracellular Leishmania donovani amastigotes. J. Biol. Chem.2003, 278, 25120–25132.Search in Google Scholar

Sun, H.; Yan, S. C.; Cheng, W. S. Interaction of antimony tartrate with the tripeptide glutathione. Eur. J. Biochem.2000, 267, 5450–5457.Search in Google Scholar

Sundar, S.; Sinha, P. R.; Agrawal, N. K.; Srivastava, R.; Rainey, P. M.; Berman, J. D.; Murray, H. W.; Singh, V. P. A cluster of cases of severe cardiotoxicity among kala-azar patients treated with a high-osmolarity lot of sodium antimony gluconate. Am. J. Trop. Med. Hyg.1998, 59, 139–143.Search in Google Scholar

Vasudevan, G.; Carter, N. S.; Drew, M. E.; Beverley, S. M.; Sanchez, M. A.; Seyfang, A.; Ullman, B.; Landfear, A. M. Cloning of Leishmania nucleoside transporter genes by rescue of a transport-deficient mutant. Proc. Natl. Acad. Sci. USA1998, 95, 9873–9878.Search in Google Scholar

Vianna, G. Treatment of tegumentary leishmaniasis by intravenous injections of tartar emetic. 7° Congresso Brasileiro de Medicina Tropical de São Paulo, São Paulo, Brasil, 1912,4, 426–428.Search in Google Scholar

Walker, J.; Saravia, N. G. Inhibition of Leishmania donovani promastigote DNA topoisomerase I and human monocyte DNA topoisomerases I and II by antimonial drugs and classical antitopoisomerase agents. J. Parasitol.2004, 90, 1155–1162.Search in Google Scholar

Webb, J. R.; McMaster, W. R. Molecular cloning and expression of a Leishmania major gene encoding a single-stranded DNA-binding protein containing nine “CCHC” zinc finger motifs. J. Biol. Chem.1993, 268, 13994–14002.Search in Google Scholar

World Health Organization, http://www.who.int/tdr/diseases/leish. (accessed August 15, 2012).Search in Google Scholar

Wyllie, S.; Fairlamb, A. H. Differential toxicity of antimonial compounds and their effects on glutathione homeostasis in a human leukaemia monocyte cell line, Biochem. Pharmacol.2006, 71, 257–267.Search in Google Scholar

Wyllie, S.; Cunningham, M. L.; Fairlamb, A. H. Dual action of antimonial drugs on thiol redox metabolism in the human pathogen Leishmania donovani. J. Biol. Chem. 2004, 279, 39925–39993.Search in Google Scholar

Wyllie, S.; Vickers, T. J.; Fairlamb, A. H. Roles of trypanothione S-transferase and tryparedoxin peroxidase in resistance to antimonials. Antimicrob. Agents Chemother.2008, 52, 1359–1365.Search in Google Scholar

Wyllie, S.; Mandal, G.; Singh, N.; Sundar, S.; Fairlamb, A. H.; Chatterjee, M. Elevated levels of tryparedoxin peroxidase in antimony unresponsive Leishmania donovani field isolates. Mol. Biochem. Parasitol.2010, 173, 162–164.Search in Google Scholar

Yan, S. C.; Li, F.; Ding, K. Y.; Sun, H. Reduction of pentavalent antimony by trypanothione and formation of a binary and ternary complex of antimony(III) and trypanothione. J. Biol. Inorg. Chem.2003, 8, 689–697.Search in Google Scholar

Yan, S.; Jin, L.; Sun, H., Gielen; E. R. T. Sb antimony in Medicine. In Metallotherapeutic Drugs and Metal-Based Diagnostic Agents: The Use of Metals in Medicine; 1st Edition. Gielen, M., Tiekink, E. R., Eds. John Wiley & Sons: New York, USA, 2005, pp. 441–461.Search in Google Scholar

Zhou, Y.; Messier, N.; Ouellette, M.; Rosen, B. P.; Mukhopadhyay, R. Leishmania major LmACR2 is a pentavalent antimony reductase that confers sensitivity to the drug Pentostam. J. Biol. Chem.2004, 279, 37445–37451.Search in Google Scholar

Received: 2012-8-15
Accepted: 2013-1-11
Published Online: 2013-02-21
Published in Print: 2013-05-01

©2013 by Walter de Gruyter Berlin Boston

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