Complexation of the anti-Trypanosoma cruzi drug benznidazole improves solubility and efficacy

Journal of Medicinal Chemistry

Volumn 51, Issue 14, 2008, Pages 4104-4114

  Silva, Jean Jerley Nogueira ^a   Pavanelli, Wander Rogério ^a   Salazar Gutierrez, Fredy R ^a   Lima, Francisco Chagas Alves ^a   Da Silva, Albérico Borges Ferreira ^a   Silva, João Santana ^a   Franco, Douglas Wagner ^a,b  

^a UNIVERSITY OF SÃO PAULO   (Brazil)

^b NONE   (Brazil)

Author keywords

[No Author keywords available]

Indexed keywords

BENZNIDAZOLE; EOSIN; HEMATOXYLIN; HYDROXYLAMINE; RUTHENIUM COMPLEX;

ACUTE TOXICITY; AMASTIGOTE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CHAGAS DISEASE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG EFFICACY; DRUG SOLUBILITY; FEMALE; HEART; IC 50; IN VITRO STUDY; IN VIVO STUDY; LD 50; MOUSE; NONHUMAN; OPTIMAL DRUG DOSE; PARASITEMIA; SKELETAL MUSCLE; STRUCTURE ACTIVITY RELATION; TREATMENT RESPONSE; TRYPANOSOMA CRUZI;

EID: 84961977839     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm701306r     Document Type: Article

References (67)

1. Engels, D.; Savioli, L. Reconsidering the Underestimated Burden Caused by Neglected Tropical Diseases. Trends Parasitol. 2006, 22, 363-366.
2. Centers for Disease Control and Prevention. Blood Donor Screening for Chagas Disease-United States 2006-2007. MMWR Morbidity and Mortality Weekly Report 2007, 56, 141-143.
3. Reesink, H. W. European Strategies Against the Parasite Transfusion Risk Risque Parasitaire, Quelles Stratégies en Europe. Trans. Clin. Biol. 2004, 12, 1-4.
4. Cerecetto, H.; González, M. Chemotherapy of Chagas' Disease: Status and New Development. Curr. Top. Med. Chem. 2002, 2, 1187-1213.
5. Sajid, M.; McKerrow, J. H. Cysteine Proteases of Parasitic Organisms. Mol. Biochem. Parasitol. 2002, 120, 1-21.
6. Docampo, R. Recent Developments in the Chemotherapy of Chagas' disease. Curr. Pharm. Des. 2001, 7, 1157-1164.
7. Boiani, M.; Boiani, L.; Denicola, A.; de Ortiz, S. T.; Serna, E.; de Bilbao, N. V.; Sanabria, L.; Yaluff, G.; Nakayama, H.; de Arias, A. R.; Veja, C.; Rolan, M.; Gomez-Barrio, A.; Cerecetto, H.; González, M. 2H-Benzimidazole 1,3-Dioxide Derivatives: A New Family of Water-Soluble Anti-trypanosomatid Agents. J. Med. Chem. 2006, 49, 3215-3224.
8. Buschini, A.; Giordani, F.; Albuquerque, C. N.; Pellacani, C.; Pelosi, G.; Rossi, C.; Zucchi, T. M.; Poli, P. Trypanocidal Nitroimidazole Derivatives: Relationships Among Chemical Structure and Genotoxic Activity. Biochem. Pharmacol. 2007, 73, 1537-1547.
9. Maya, J. D.; Cassels, B. K.; Iturriaga-Vásquez, P.; Ferreira, J.; Faúndez, M.; Galanti, N.; Morello, A. Mode of Action of Natural and Synthetic Drugs Against Trypanosoma cruzi and their Interaction with the Mammalian Host. Comp. Biochem. Physiol. 2007, 146, 601-620.
10. Castro, J. A.; Meca, M. M.; Bartel, L. C. Toxic Side Effect of Drugs Used to Treat Chagas' Disease (American trypanosomiasis). Human. Exp. Toxicol. 2006, 25, 471-479.
11. Martinez-Díaz, R. A.; Escario, J. A.; Nogal-Ruiz, J. J.; Gómez-Barrio, A. Biological Characterization of Trypanosoma cruzi Strains. Mem. Inst. Oswaldo Cruz 2001, 96, 53-59.
12. Sanchez-Delgado, R. A.; Anzellotti, A. Metal Complexes as Chemotherapeutic Agents Against Tropical Diseases: Trypanosomiasis, Malaria and Leishmaniasis. Mini. Rev. Med. Chem. 2004, 4, 23-30.
13. Otero, L.; Vieites, M.; Bioani, 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 Antrypanosomal Agents Based on Palladium Nitrofurylthiosemicarbazone Complexes: DNA and Redox Metabolism as Potential Therapeutic Targets. J. Med. Chem. 2006, 49, 3322-3331.
14. Sánchez-Delgado, R. A.; Navarro, M.; Lazardi, K.; Atencio, R.; Capparelli, M.; Vargas, F.; Urbina, J. A.; Bouillez, A.; Noels, A. F.; Mais, D. Toward a Novel Metal-Based Chemotherapy Against Tropical Diseases. Part 4. Synthesis and Characterization of New Metal-Clotrimazole Complexes and Evaluation of Their Activity Against Trypanosoma cruzi. Inorg. Chim. Acta. 1998, 528-540.
15. Navarro, M.; Lahmann, 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, 2319-2325.
16. Tfouni, E.; Krieger, M.; McGarvey, B.; Franco, D. W. Structure, Chemical and Photochemical Reactivity and Biological Activity of Some Ruthenium Nitrosyl Complexes. Coord. Chem. Rev. 2003, 236, 57-69.
17. Silva, J. J. N.; Osakabe, A. L.; Pavanelli, W. R.; Silva, J. S.; Franco, D. W. In Vitro and in Vivo Antiproliferative and Trypanocidal Activities of Ruthenium NO Donors. Br. J. Pharmacol. 2007, 152, 112-121.
18. Vespa, G. N. R.; Cunha, F. Q.; Silva, J. S. Nitric Oxide is Involved in Control of Trypanosoma cruzi-Induced Parasitemia and Direct Kills of the Parasite in vitro. Infect. Immun. 1994, 62, 5177-5182.
19. Isied, S. S.; Taube, H. Effects of Sulfur Dioxide, Bisulfite(1-), and Sulfite(2-) as Auxiliary Ligands on the Reactivity of Ammineruthenium(II)-ligand Bonds. Inorg. Chem. 1974, 13, 1545-1551.
20. Brown, G. M.; Sutton, J. E.; Taube, H. Binding of a Tetraammineruthenium Complex to Imidazole and Purine Derivatives under Equilibrium Conditions. J. Am. Chem. Soc. 1978, 26, 2767-2774.
21. Borges, S. S. S.; Davanzo, C. U.; Castellano, E. E.; Z-Zchpector, J.; Silva, S. C.; Franco, D. W. Ruthenium Nitrosyl Complexes with N-heterocyclic Ligands. Inorg. Chem. 1998, 37, 2670-2677.
22. Maya, J. D.; Bollo, S.; Nuñez-Vergara, L. J.; Squella, J. A.; Repetto, Y.; Morello, A.; Périé, J.; Chauvière, G. Trypanosoma cruzi: Effect and Mode of Action of Nitroimidazole and Nitrofuran Derivatives. Biochem. Pharmacol. 2003, 65, 999-1006.
23. Matsubara, T.; Ford, P. Some Applications of Cyclic Voltammetry to the Reactions and Properties of Ruthenium Ammine Complexes. Reduction Potentials and Rate Studies. Inorg. Chem. 1976, 15, 1107-1110.
24. Bollo, S.; Núñez-Vergara, L. J.; Bontá, M.; Chauviere, G.; Périé, J.; Squella, J. A. Cyclic Voltammetric Studies on Nitro Radical Anion Formation From Megazol and Some Related Nitroimidazole Derivatives. J. Electroanal. Chem. 2001, 511, 46-54.
25. Toledo, J. C.; Lima Neto, B. S.; Franco, D. W. Mutual Effects in the Chemical Properties of the Ruthenium Metal Center and Ancillary Ligands upon Coordination. Coord. Chem. Rev. 2005, 249, 419-431.
26. Clarke, M. J.; Taube, H. Pentaammineruthenium-guanine Complexes. J. Am. Chem. Soc. 1974, 96, 5413-5419.
27. Franco, D. W.; Taube, H. Triethyl Phosphite as a Ligand on Ruthenium(II). Inorg. Chem. 1978, 17, 571-578.
28. Vogt, L. H.; Katz, J. L.; Wiberley, S. E. The Crystal and Molecular Structure of Ruthenium-Sulfur Dioxide Coordination Compounds. I. Chlorotetraammine(Sulfur Dioxide)Ruthenium(II) Chloride. Inorg. Chem. 1965, 4, 1157-1163.
29. Nothenberg, M. S.; Takeda, G. K. F.; Najjar, R. Adducts of Nitroimidazoles Derivatives with Rhodium(II) Carboxylates: Synthesis, Characterization, and Evaluation of Antichagassic Activities. J. Inorg. Biochem. 1991, 42, 217-229.
30. Lamas, M. C.; Villaggi, L.; Nocito, I.; Bassani, G.; Leonardi, D.; Pascutti, F.; Serra, E.; Salomón, C. J. Development of Parenteral Formulations and Evaluation of the Biological Activity of the Trypanocide Drug Benznidazole. Int. J. Pharm. 2006, 307, 239-243.
31. Freshney, R. Culture of Animal Cells: A Manual of Basic Technique; Alan R. Liss, Inc.: New York, 1987, pp 117.
32. Lyons, A. B.; Parish, C. R. Determination of Lymphocyte Division by Flow Cytometry. J. Immunol. Methods 1994, 171, 131-137.
33. Melo, P. S.; Durán, N.; Haun, M. Cytotoxicity of Prodigiosin and Benznidazole on V79 Cells. Toxicol. Lett. 2000, 116, 237-242.
34. Bruce, R. D. An Up-and-Down Procedure For Acute Toxicity Testing. Fundam. Appl. Toxicol. 1985, 5, 151-157.
35. Castro, S. L.; Meirelles, M. N. L. Effect of Drugs on Trypanosoma cruzi and on its Interaction with Heart Muscle Cell in Vitro. Mem. Inst. Oswaldo Cruz 1986, 82, 209-218.
36. Silva, J. J. N.; Pavanelli, W. R.; Silva, J. S.; Franco, D. W. Experimental Chemotherapy Against Trypanosoma cruzi Infection Using Ruthenium NO-donors. Antimicrob. Agents Chemother. 2007, . submitted.
37. Silva, R. S. F.; Costa, E. M.; Trindade, U. L. T.; Teixeira, D. V.; Pinto, M. C. F. R.; Santos, G. L.; Malta, V. R. S.; De Simone, C. A.; Pinto, A. V.; De Castro, S. L. Synthesis of Naphthofuranquinones with Activity Against Trypanosoma cruzi. Eur. J. Med. Chem. 2006, 41, 526-530.
38. Molina, J.; Martins-Filho, O.; Brener, Z.; Romanha, A. J.; Loebenberg, D.; Urbina, J. A. Activity of the Triazole Derivative SCH 56592 (Posaconazole) Against Drug-resistant Strains of the Protozoan Parasite Trypanosoma (Schizotrypanum) cruzi in Immunocompetent and Immunosuppressed Murine Hosts. Antimicrob. Agents Chemother. 2000, 44, 150-155.
39. Ferraz, M. L.; Gazzinelli, R. T.; Alves, R. O.; Urbina, J. A.; Romanha, A. J. The Anti-Trypanosoma cruzi Activity of Posaconazole in a Murine Model of Acute Chagas' Disease is Less Dependent on Gamma Interferon Than That of Benznidazole. Antimicrob. Agents Chemother. 2007, 51, 1359-1364.
40. Sanchez-Delgado, R.; Navarro, M.; Lazardi, K.; Atencio, R.; Capparelli, M.; Vargas, F.; Urbina, J. A.; Bouillez, A.; Noels, A. F.; Mais, D. Toward a Novel Metal Based Chemotherapy Against Tropical Disease 4. Synthesis and Characterization of a New Metal-Clotrimazole Complexes and Evaluation of Their Activity Against Trypanosoma cruzi. Inorg. Chim. Acta 1998, 275-276, 528-540.
41. Otero, L.; Nobia, P.; Gambino, D.; Crecetto, H.; González, M.; Ellena, J. A.; Piro, O. E. Synthesis and Characterization of New Ruthenium Complexes with Active Ligands Against Chagas' Disease. Inorg. Chim. Acta 2003, 344, 85-94.
42. Petray, P. B.; Morilla, M. J.; Corral, R. S.; Romero, E. L. In Vitro Activity of Etanidazole Against the Protozoan Parasite Trypanosoma cruzi. Mem. Inst. Oswaldo Cruz 2004, 99, 233-235.
43. Squella, J. A.; Letelier, M. E.; Lindermeyer, L.; Nuñez-Vergara, L. J. Redox Behaviour of Nifuroxazide: Generation of the One-Electron Reduction Product. Chem. - Biol. Interact. 1996, 99, 227-238.
44. Cerecetto, H.; Di Maio, R.; González, M.; Risso, M.; Sagrera, G.; Seoane, G.; Denicola, A.; Peluffo, G.; Quijano, C.; Stoppani, A.; Paulino, M.; Olea-Azar, C.; Basombrio, M. A. Synthesis and Antitrypanosomal Evaluation of E-isomers of 5-Nitro-2-furaldehyde and 5-Nitrothiophene-2-carboxaldehyde Semicarbazone Derivatives. Structure-Activity Relationships. Eur. J. Med. Chem. 2000, 35, 343-350.
45. Dias, L. R. S.; Santo, M. B.; Albuquerque, S.; Castro, H. C.; Souza, A. M. T.; Freitas, A. C. C.; DiVaio, M. A. V.; Cabral, L. M.; Rodrigues, C. R. Synthesis, in Vitro Evaluation, and SAR Studies of a Potential Antichagasic 1H-Pyrazolo[3,4-b]pyridine Series. Bioorg. Med. Chem. 2007, 15, 211-219.
46. Porcal, W.; Paola, H.; Aguire, G.; Bioani, L.; Bioani, M.; Merlino, A.; Ferreira, A.; Di Maio, R.; Castro, A.; González, M.; Cerecetto, H. Second Generation of 5-Ethenylbenzofuroxan Derivatives as Inhibitors of Trypanosoma cruzi Growth: Synthesis, Biological Evaluation, and Structure-Activity Relationships. Bioorg. Med. Chem. 2007, 15, 2768-2781.
47. Marin-Neto, J. A.; Cunha-Neto, E.; Maciel, B. C.; Simões, M. V. Phatogenesis of Chronic Chagas' Heart Disease. Circulation. 2007, 115, 1109-1123.
48. Garcia, S.; Ramos, C. O.; Senra, J. F.; Vilas-Boas, F.; Rodrigues, M. M.; Campos-de-Carvalho, A. C.; Ribeiro-Dos-Santos, R.; Soares, M. B. Treatment with Benznidazole During the Chronic Phase of Experimental Chagas' Disease Decreases Cardiac Alterations. Antimicrob. Agents Chemother. 2005, 49, 1521-1528.
49. Perrin, D. D.; Armarego, W. L. F.; Perrin, D. R. Purification of Laboratory Chemicals; Pergamon Press: Elmsford, NY, 1980.
50. Shriver, D. F. The Manipulation of Air-Sensitive Compound. McGraw-Hill: New York, 1969.
51. Clarke, M. J. Electrochemistry, Synthesis, and Spectra of Pentaammineruthenium(III) Complexes of Cytidine, Adenosine, and Related Ligands. J. Am. Chem. Soc. 1978, 100, 5068-5075.
52. Galia, E.; Nicolaides, E.; Horter, D.; Lobenberg, R.; Reppas, C.; Dressman, J. B. Evaluation of Various Dissolution Media for Predicting In Vivo Performance of Class I and II Drugs. Pharm. Res. 1998, 15, 698-705.
53. Kasim, N. A.; Whitehouse, M.; Ramachandran, C.; Bermejo, M.; Lennernäs, H.; Hussain, A. S.; Jungiger, H. E.; Stavchansky, S. A.; Midha, K. K.; Shah, V. P.; Amidon, G. L. Molecular Properties of WHO Essential Drugs and Provisional Biopharmaceutical Classification. Mol. Pharm. 2004, 1, 85-96.
54. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03, revision C.02; Gaussian, Inc.: Wallingford, CT, 2004.
55. Becke, A. D. Density-Functional Thermochemistry. III. The Role of Exact Exchange. J. Chem. Phys. 1993, 98, 5648-5652.
56. Lee, C.; Yang, W.; Parr, R. G. Development of the Colle-Salvetti Correlation-Energy Formula into a Functional of the Electron Density. Phys. Rev. B 1988, 37, 785-789.
57. Farkas, O.; Schlegel, H. B. Methods for Optimizing Large Molecules. II. Quadratic Search. J. Chem. Phys. 1999, 111, 10806-10814.
58. Becke, A. D. Density-Functional Exchange-Energy Approximation with Correct Asymptotic Behavior. Phys. Rev. A 1988, 38, 3098-3100.
59. Glendening, E. D.; Badenhoop, J. K.; Reed, A. E.; Carpenter, J. E.; Bohmann, J. A.; Morales, C. M.; Weinhold, F. NBO 3.0; Theoretical Chemistry Institute: Madison, WI, 1998.
60. Cances, E.; Mennucci, B.; Tomasi, J. A New Integral Equation Formalism for the Polarizable Continuum Model: Theoretical Background and Applications to Isotropic and Anisotropic Dielectrics. J. Chem. Phys. 1997, 107, 3032-3041.
61. Miertus, S.; Scrocco, E.; Tomasi, J. Electrostatic Interaction of a Solute with a Continuum. A Direct Utilization of ab Initio Molecular Potentials for the Prevision of Solvent Effects. Chem. Phys. 1981, 55, 117-129.
62. Foresman, J. B.; Frisch, A. E. Exploring Chemistry With Electronic Structure Methods; Gaussian, Inc.: Pittsburgh, PA, 1998.
63. Zimmermann, M. Ethical Guidelines for Investigations of Experimental Pain in Conscious Animals. Pain 1983, 16, 109-110.
64. Russell, W. M. S.; Burch, R. L. The Principles of Humane Experimental Technique; Hyperion Books: New York, 1992.
65. Brener, Z. Therapeutic Activity and Criterion of Cure on Mice Experimentally Infected with Trypanosoma cruzi. Rev. Inst. Med. Trop. 1962, 4, 389-396.
66. Cunnick, J.; Kaur, P.; Cho, Y.; Groffen, J.; Heisterkamp, N. Use of Bone Marrow-Derived Macrophages to Model Murine Innate Immune Responses. J. Immunol. Methods 2006, 311, 96-105.
67. Coder, D. M. Assessment of Cell Viability. In Current Protocols in Cytometry; Robinson, J. P., Ed.; International Society for Analytical Cytology: Bethesda, MD, 2008; pp 447-458.