Searching for new chemotherapies for tropical diseases: Ruthenium-clotrimazole complexes display high in vitro activity against Leishmania major and Trypanosoma cruzi and low toxicity toward normal mammalian cells

Journal of Medicinal Chemistry

Volumn 55, Issue 8, 2012, Pages 3867-3877

  Martínez, Alberto ^a   Carreon, Teresia ^b   Iniguez, Eva ^b   Anzellotti, Atilio ^c   Sánchez, Antonio ^a   Tyan, Marina ^a   Sattler, Aaron ^d   Herrera, Linda ^b   Maldonado, Rosa A ^b   Sánchez Delgado, Roberto A ^a  

^a CITY UNIVERSITY OF NEW YORK   (United States)

^b UNIVERSITY OF TEXAS AT EL PASO   (United States)

^c INSTITUTO VENEZOLANO DE INVESTIGACIONES CIENTÍFICAS   (Venezuela)

^d Och Spine at New York Presbyterian Hospitals   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CLOTRIMAZOLE; RUTHENIUM COMPLEX;

AMASTIGOTE; ANTIMICROBIAL ACTIVITY; ARTICLE; DRUG SYNTHESIS; EPIMASTIGOTE; HUMAN; HUMAN CELL; IN VITRO STUDY; LEISHMANIA MAJOR; MACROPHAGE; MAMMAL CELL; MOUSE; NONHUMAN; OSTEOBLAST; PROMASTIGOTE; TROPICAL DISEASE; TRYPANOSOMA CRUZI;

ANIMALS; ANTIPROTOZOAL AGENTS; CELL LINE; CLOTRIMAZOLE; CRYSTALLOGRAPHY, X-RAY; HUMANS; LEISHMANIA MAJOR; MICE; ORGANOMETALLIC COMPOUNDS; RUTHENIUM; TRYPANOSOMA CRUZI;

EID: 84860285787     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm300070h     Document Type: Article

References (77)

1. den Boer, M.; Argaw, D.; Jannin, J.; Alvar, J. Leishmaniasis impact and treatment access Clin. Microbiol. Infect. 2011, 17 (10) 1471-1477
2. WHO, Control of leishmaniases. Report of a WHO expert committee. W.H.O. Tech. Rep. Ser. 2010, 949, 1-186.
3. WHO Control of Chagas disease W.H.O. Tech. Rep. Ser. 2002, 905, 24-28
4. Barrett, M. P.; Burchmore, R. J. S.; Stich, A.; Lazzari, J. O.; Frasch, A. C.; Cazzulo, J. J.; Krishna, S. The trypanosomiases Lancet 2003, 362 (9394) 1469-1480 (Pubitemid 37352887)
5. Dias, J. C.; Silveira, A. C.; Schofield, C. J. The impact of Chagas disease control in Latin America: a review Mem. Inst. Oswaldo Cruz 2002, 97 (5) 603-612 (Pubitemid 135746072)
6. Hotez, P. J.; Bottazzi, M. E.; Franco-Paredes, C.; Ault, S. K.; Periago, M. R. The Neglected Tropical Diseases of Latin America and the Caribbean: A Review of Disease Burden and Distribution and a Roadmap for Control and Elimination PLoS Negl. Trop. Dis. 2008, 2 (9) e300
7. Kirchhoff, L. V. Epidemiology of American trypanosomiasis (Chagas disease) Adv. Parasitol. 2011, 75, 1-18
8. Bern, C.; Kjos, S.; Yabsley, M. J.; Montgomery, S. P. Trypanosoma cruzi and Chagas Disease in the United States Clin. Microbiol. Rev. 2011, 24 (4) 655-681
9. Schmunis, G. A. Epidemiology of Chagas disease in non-endemic countries: the role of international migration Mem. Inst. Oswaldo Cruz 2007, 102 (Suppl 1) 75-85 (Pubitemid 350146006)
10. Diaz, J. H., Chagas disease in the United States: a cause for concern in Louisiana? J. La. State Med. Soc. 2007, 159 (1), 21-3, 25-9.
11. Croft, S. L.; Barrett, M. P.; Urbina, J. A. Chemotherapy of trypanosomiases and leishmaniasis Trends Parasitol. 2005, 21 (11) 508-512 (Pubitemid 41447021)
12. Selzer, P. M. Antiparasitic and Antibacterial Drug Discovery; Wiley-VCH: Weinheim, 2009.
13. Ponte-Sucre, A.; Diaz, E.; Padron-Nieves, M. Drug Resistance in Leishmania Parasites: Consequences, Molecular Mechanisms and Possible Treatments; Springer: Vienna, 2012.
14. Polonio, T.; Efferth, T. Leishmaniasis: drug resistance and natural products (review) Int. J. Mol. Med. 2008, 22 (3) 277-286
15. Urbina, J. A. Specific chemotherapy of Chagas disease: Relevance, current limitations and new approaches Acta Trop. 2010, 115 (1-2) 55-68
16. Urbina, J. A. New Insights in Chagas Disease Treatment Drugs Fut. 2010, 5 (35) 409-419
17. Urbina, J. A. Ergosterol biosynthesis and drug development for Chagas disease Mem. Inst. Oswaldo Cruz 2009, 104 (Suppl. 1) 311-318
18. Urbina, J. A.; Payares, G.; Molina, J.; Sanoja, C.; Liendo, A.; Lazardi, K.; Piras, M. M.; Piras, R.; Perez, N.; Wincker, P.; Ryley, J. F. Cure of Short- and Long-Term Experimental Chagas Disease Using D0870 Science 1996, 273 (5277) 969-971 (Pubitemid 26275176)
19. Sánchez-Delgado, R. A.; Anzellotti, A.; Suárez, L. Metal complexes as chemotherapeutic agents against tropical diseases: malaria, trypanosiomiasis and leishmaniasis. In Metal Ions in Biological Systems; Siegel, H.; Siegel, A., Eds.; Marcel Dekker, Inc.: New York, 2004; Vol. 41, pp 379-419.
20. Sánchez-Delgado, R. A.; Anzellotti, A. Metal Complexes as Chemotherapeutic Agents Against Tropical Diseases: Trypanosomiasis, Malaria and Leishmaniasis Mini Rev. Med. Chem. 2004, 4 (1) 23-30 (Pubitemid 38842591)
21. Navarro, M.; Gabbiani, C.; Messori, L.; Gambino, D. Metal-based drugs for malaria, trypanosomiasis and leishmaniasis: recent achievements and perspectives Drug Discovery Today 2010, 15 (23-24) 1070-1078
22. Fricker, S. P.; Mosi, R. M.; Cameron, B. R.; Baird, I.; Zhu, Y.; Anastassov, V.; Cox, J.; Doyle, P. S.; Hansell, E.; Lau, G.; Langille, J.; Olsen, M.; Qin, L.; Skerlj, R.; Wong, R. S. Y.; Santucci, Z.; McKerrow, J. H. Metal compounds for the treatment of parasitic diseases J. Inorg. Biochem. 2008, 102, 1839-1845
23. O'Sullivan, M. C. The battle against trypanosomiasis and leishmaniasis: Metal-based and natural product inhibitors of trypanothione reductase Curr. Med. Chem.: Anti-Infect. Agents 2005, 4, 355-378 (Pubitemid 41264280)
24. Alessio, E. Bioinorganic Medicinal Chemistry; Wiley-VCH: Weinheim, 2011.
25. 2 J. Med. Chem. 1993, 36 (14) 2041-2043 (Pubitemid 23230336)
26. Sánchez-Delgado, R. A.; Navarro, M.; Lazardi, K.; Atencio, R.; Capparelli, M.; Vargas, F.; Urbina, J. A.; Bouillez, A.; Noels, A. F.; Masi, D. Toward a novel metal based chemotherapy against tropical diseases 4. Synthesis and characterization of new metal-clotrimazole complexes and evaluation of their activity against Trypanosoma cruzi Inorg. Chim. Acta 1998, 275-276, 528-540 (Pubitemid 128351381)
27. Navarro, M.; Lehmann, T.; Cisneros-Fajardo, E. J.; Fuentes, A.; Sánchez-Delgado, R. A.; Silva, P.; Urbina, J. A. Toward a novel metal-based chemotherapy against tropical diseases.: Part 5. Synthesis and characterization of new Ru(II) and Ru(III) clotrimazole and ketoconazole complexes and evaluation of their activity against Trypanosoma cruzi Polyhedron 2000, 19 (22-23) 2319-2325 (Pubitemid 32038875)
28. Navarro, M.; Cisneros-Fajardo, E. J.; Lehmann, T.; Sánchez- Delgado, R. A.; Atencio, R.; Silva, P.; Lira, R.; Urbina, J. A. Toward a Novel Metal-Based Chemotherapy against Tropical Diseases. 6. Synthesis and Characterization of New Copper(II) and Gold(I) Clotrimazole and Ketoconazole Complexes and Evaluation of Their Activity against Trypanosoma cruzi Inorg. Chem. 2001, 40 (27) 6879-6884
29. 2 J. Biol. Inorg. Chem. 2008, 13 (5) 703-712
30. Rajapakse, C. S. K.; Martínez, A.; Naoulou, B.; Jarzecki, A. A.; Suárez, L.; Deregnaucourt, C.; Sinou, V.; Schrével, J.; Musi, E.; Ambrosini, G.; Schwartz, G. K.; Sánchez-Delgado, R. A. Synthesis, Characterization, and in vitro Antimalarial and Antitumor Activity of New Ruthenium(II) Complexes of Chloroquine Inorg. Chem. 2009, 48 (3) 1122-1131
31. Martínez, A.; Rajapakse, C.; Jalloh, D.; Dautriche, C.; Sánchez-Delgado, R. A. The antimalarial activity of Ru-chloroquine complexes against resistant Plasmodium falciparum is related to lipophilicity, basicity, and heme aggregation inhibition ability near water-octanol interfaces J. Biol. Inorg. Chem. 2009, 14 (6) 863-871
32. Otero, L.; Vieites, M.; Boiani, L.; Denicola, A.; Rigol, C.; Opazo, L.; Olea-Azar, C.; Maya, J. D.; Morello, A.; Krauth-Siegel, R. L.; Piro, O. E.; Castellano, E.; González, M.; Gambino, D.; Cerecetto, H. Novel Antitrypanosomal Agents Based on Palladium Nitrofurylthiosemicarbazone Complexes: DNA and Redox Metabolism as Potential Therapeutic Targets J. Med. Chem. 2006, 49 (11) 3322-3331 (Pubitemid 43830530)
33. Vieites, M.; Otero, L.; Santos, D.; Olea-Azar, C.; Norambuena, E.; Aguirre, G.; Cerecetto, H.; González, M.; Kemmerling, U.; Morello, A.; Diego Maya, J.; Gambino, D. Platinum-based complexes of bioactive 3-(5-nitrofuryl)acroleine thiosemicarbazones showing anti-Trypanosoma cruzi activity J. Inorg. Biochem. 2009, 103 (3) 411-418
34. Vieites, M.; Otero, L.; Santos, D.; Toloza, J.; Figueroa, R.; Norambuena, E.; Olea-Azar, C.; Aguirre, G.; Cerecetto, H.; González, M.; Morello, A.; Maya, J. D.; Garat, B.; Gambino, D. Platinum(II) metal complexes as potential anti-Trypanosoma cruzi agents J. Inorg. Biochem. 2008, 102 (5-6) 1033-1043
35. Demoro, B.; Sarniguet, C.; Sánchez-Delgado, R.; Rossi, M.; Liebowitz, D.; Caruso, F.; Olea-Azar, C.; Moreno, V.; Medeiros, A.; Comini, M. A.; Otero, L.; Gambino, D. New organoruthenium complexes with bioactive thiosemicarbazones as co-ligands: potential anti-trypanosomal agents Dalton Trans. 2012, 41, 1534-1543
36. 2(thiosemicarbazone)] complexes (M = Pt/Pd): Support for multiple mechanisms of antichagasic action excluding DNA-bonding in vivo Eur. J. Med. Chem. 2011, 46, 2639-2651
37. Vieites, M.; Smircich, P.; Parajon-Costa, B.; Rodriguez, J.; Galaz, V.; Olea-Azar, C.; Otero, L.; Aguirre, G.; Cerecetto, H.; Gonzalez, M.; Gomez-Barrio, A.; Garat, B.; Gambino, D. Potent in vitro anti-Trypanosoma cruzi activity of pyridine-2-thiol N-oxide metal complexes having an inhibitory effect on parasite-specific fumarate reductase J. Biol. Inorg. Chem. 2008, 13, 723-735
38. Benitez, J.; Guggeri, L.; Tomaz, I.; Pessoa, J. C.; Moreno, V.; Lorenzo, J.; Aviles, F. X.; Garat, B.; Gambino, D. A novel vanadyl complex with a polypyridyl DNA intercalator as ligand: A potential anti-protozoa and anti-tumor agent J. Inorg. Biochem. 2009, 103, 1386-1394
39. Rodrigues, C.; Batista, A. A.; Ellena, J.; Castellano, E. E.; Benitez, D.; Cerecetto, H.; Gonzalez, M.; Teixeira, L. R.; Beraldo, H. Coordination of nitro-thiosemicarbazones to ruthenium(II) as a strategy for anti-trypanosomal activity improvement Eur. J. Med. Chem. 2010, 45, 2847-2853
40. Donnici, C. L.; Araujo, M. H.; Oliveira, H. S.; Moreira, D. R. M.; Pereira, V. R. A.; Souza, M. d. A.; Brelaz, d. C. M. C. A.; Leite, A. C. L. Ruthenium complexes endowed with potent anti-Trypanosoma cruzi activity: Synthesis, biological characterization and structure-activity relationships Bioorg. Med. Chem. 2009, 17, 5038-5043
41. 2+ (M = Pd or Pt) moiety Synthesis, Characterization and anti-Tripanosoma Cruzi activity J. Inorg. Biochem. 2010, 104, 1276-1282
42. Demoro, B.; Caruso, F.; Rossi, M.; Benitez, D.; Gonzalez, M.; Cerecetto, H.; Parajon-Costa, B.; Castiglioni, J.; Galizzi, M.; Docampo, R.; Otero, L.; Gambino, D. Risedronate metal complexes potentially active against Chagas disease J. Inorg. Biochem. 2010, 104, 1252-1258
43. Caballero, A. B.; Marin, C.; Rodriguez-Dieguez, A.; Ramirez-Macias, I.; Barea, E.; Sanchez-Moreno, M.; Salas, J. M. In vitro and in vivo antiparasital activity against Trypanosoma cruzi of three novel 5-methyl-1,2,4-triazolo[1,5-a] pyrimidin-7(4H)-one-based complexes J. Inorg. Biochem. 2011, 105, 770-776
44. Batista, D. d. G. J.; da, S. P. B; Stivanin, L.; Lachter, D. R.; Silva, R. S.; Felcman, J.; Louro, S. R. W.; Teixeira, L. R.; Soeiro, M. d. N. C. Co(II), Mn(II) and Cu(II) complexes of fluoroquinolones: Synthesis, spectroscopical studies and biological evaluation against Trypanosoma cruzi Polyhedron 2011, 30, 1718-1725
45. 3. DNA interaction studies and biological activity against Leishmania (L) mexicana J. Inorg. Biochem. 2007, 101 (1) 111-116 (Pubitemid 44883313)
46. Navarro, M.; Cisneros-Fajardo, E. J.; Marchan, E. New silver polypyridyl complexes: synthesis, characterization, and biological activity on Leishmania mexicana Arzneim.-Forsch. 2006, 56, 600-604 (Pubitemid 44358652)
47. Baiocco, P.; Ilari, A.; Ceci, P.; Orsini, S.; Gramiccia, M.; Di, M. T.; Colotti, G. Inhibitory Effect of Silver Nanoparticles on Trypanothione Reductase Activity and Leishmania infantum Proliferation ACS Med. Chem. Lett. 2011, 2, 230-233
48. Everson, d. S. L.; Teixeira, d. S. P., Jr.; Maciel, E. N.; Nunes, R. K.; Eger, I.; Steindel, M.; Rebelo, R. A. In vitro antiprotozoal evaluation of zinc and copper complexes based on sulfonamides containing 8-aminoquinoline ligands Lett. Drug Des. Discovery 2010, 7, 679-685
49. Evans, I. P.; Spencer, A.; Wilkinson, G. Dichlorotetrakis(dimethyl sulphoxide)ruthenium(II) and its use as a source material for some new ruthenium(II) complexes J. Chem. Soc., Dalton Trans. 1973, 2, 204-209
50. Alessio, E.; Balducci, G.; Calligaris, M.; Costa, G.; Attia, W. M.; Mestroni, G. Synthesis, molecular structure, and chemical behavior of hydrogen trans -bis(dimethyl sulfoxide)tetrachlororuthenate(III) and mer -trichlorotris(dimethyl sulfoxide)ruthenium(III): the first fully characterized chloride-dimethyl sulfoxide-ruthenium(III) complexes Inorg. Chem. 1991, 30 (4) 609-618
51. 2O Inorg. Chim. Acta 1991, 187 (1) 39-50
52. 4 Inorg. Chem. 1996, 35 (9) 2538-2545 (Pubitemid 126456101)
53. Sens, C.; Rodríguez, M.; Romero, I.; Llobet, A. Synthesis, Structure, spectroscopy, Photochemical, Redox and Catalytic Properties of New Ru(II) Isomeric Complexes Containing Dimethylsulfoxide, Chloro and the Dinucleating bis-2-pyridylpyrazole ligands Inorg. Chem. 2003, 42 (6) 2049-2048
54. 2 Inorg. Chem. 1996, 35 (8) 2384-2389 (Pubitemid 126456003)
55. Marzilli, L. G.; Iwamoto, M.; Alessio, E.; Hansen, L.; Calligaris, M. The Rare Head-to-Head Conformation of Untethered Lopsided Ligands Discovered in Both Solution and Solid States of 1,5,6-Trimethylbenzimidazole Re(V) and Ru(II) Complexes J. Am. Chem. Soc. 1994, 116 (2) 815-816 (Pubitemid 24980524)
56. 3) Inorg. Chim. Acta 1993, 203 (2) 205-217
57. 2O)(dmso-S)(dmtp)] (dmtp = 5,7-Dimethyl[1,2,4]triazolo[1,5-a] pyrimidine) J. Med. Chem. 2004, 47 (5) 1110-1121
58. Anderson, C. M.; Herman, A.; Rochon, F. D. Synthesis and characterization of ionic Ru(III) complexes containing dimethylsulfoxide and dinitrogen heterocyclic ligands Polyhedron 2007, 26 (14) 3661-3668
59. - Inorg. Chem. 2008, 47 (14) 6513-6523
60. Peti, W.; Pieper, T.; Sommer, M.; Keppler, B. K.; Giester, G. Synthesis of Tumor-Inhibiting Complex Salts Containing the Anion trans- Tetrachlorobis(indazole)ruthenate(III) and Crystal Structure of the Tetraphenylphosphonium Salt Eur. J. Inorg. Chem. 1999, 1999, 1551-1555
61. Lipponer, K. G.; Vogel, E.; Keppler, B. K. Synthesis, Characterization and Solution Chemistry of trans-Indazoliumtetrachlorobis(Indazole)Ruthenate(III) , a New Anticancer Ruthenium Complex. IR, UV, NMR, HPLC Investigations and Antitumor Activity. Crystal Structures of trans-1-Methyl- Indazoliumtetrachlorobis-(1-Methylindazole)Ruthenate(III) and its Hydrolysis Product trans-Monoaquatrichlorobis-(1-Methylindazole)-Ruthenate(III) Met.-Based Drugs 1996, 3 (5) 243-260
62. Morris, R. E.; Aird, R. E.; del Socorro Murdoch, P.; Chen, H.; Cummings, J.; Hughes, N. D.; Parsons, S.; Parkin, A.; Boyd, G.; Jodrell, D. I.; Sadler, P. J. Inhibition of Cancer Cell Growth by Ruthenium(II) Arene Complexes J. Med. Chem. 2001, 44 (22) 3616-3621 (Pubitemid 33026669)
63. 2] Complexes Inorg. Chem. 2006, 45 (23) 9558-9568
64. Fernández, R.; Melchart, M.; Habtemariam, A.; Parsons, S.; Sadler, P. J. Use of Chelating Ligands to Tune the Reactive Site of Half-Sandwich Ruthenium(II)-Arene Anticancer Complexes Chem.-Eur. J. 2004, 10 (20) 5173-5179
65. 6-Arene Imidazole Complexes J. Med. Chem. 2006, 49 (18) 5552-5561 (Pubitemid 44376319)
66. Bennett, M. A.; Huang, T. N.; Matheson, T. W.; Smith, A. K. Inorg. Synth. 1982, 21, 74-78.
67. Crabtree, R. H.; Pearman, A. J. Arene-ruthenium complexes containing nitrogen donor ligands J. Organomet. Chem. 1977, 141 (3) 325-330
68. 13C) studies of ruthenium(II) complexes containing pyrazolyl ligands J. Chem. Soc., Dalton Trans. 1990, 4, 1463-1476
69. Sheldrick, G. M. SHELXTL, An Integrated System for Solving, Refining and Displaying Crystal Structures from Diffraction Data; University of Göttingen: Göttingen, Federal Republic of Germany, 1981.
70. Sheldrick, G. M. A short history of SHELX Acta Crystallogr., Sect A: Found. Crystallogr. 2008, 64 (Pt 1) 112-122
71. Lara, D.; Feng, Y.; Bader, J.; Savage, P. B.; Maldonado, R. A. Anti-trypanosomatid activity of ceraginins J. Parasitol. 2010, 96 (3) 638-642
72. Andrews, N. W.; Colli, W. Adhesion and interiorization of Trypanosoma cruzi in mammalian cells J. Protozool. 1982, 29 (2) 264-269 (Pubitemid 12025798)
73. Camargo, E. P. Growth And Differentiation In Trypanosoma Cruzi. I. Origin Of Metacyclic Trypanosomes In Liquid Media Rev. Inst. Med. Trop. Sao Paulo 1964, 12, 93-100
74. Thalhofer, C. J.; Graff, J. W.; Love-Homan, L.; Hickerson, S. M.; Craft, N.; Beverley, S. M.; Wilson, M. E. In vivo imaging of transgenic Leishmania parasites in a live host J. Vis. Exp. 2010, 41) e1980
75. Uphoff, C. C.; Drexler, H. G. Detection of mycoplasma contaminations Methods Mol. Biol. 2005, 290, 13-23
76. Nohara, L. L.; Lema, C.; Bader, J. O.; Aguilera, R. J.; Almeida, I. C. High-content imaging for automated determination of host-cell infection rate by the intracellular parasite Trypanosoma cruzi Parasitol. Int. 2010, 59 (4) 565-570
77. Zhang, J. H.; Chung, T. D. Y.; Oldenburg, K. R. A simple statistical parameter for use in evaluation and validation of high throughput screening assays J. Biomol. Screen. 1999, 4, 67-73 (Pubitemid 29278954)