Cysteine peptidase inhibitors in trypanosomatid parasites

Current Medicinal Chemistry

Volumn 20, Issue 25, 2013, Pages 3152-3173

  Lima, A P C A ^a   Reis, F C G ^a   Costa, T F R ^a  

^a FEDERAL UNIVERSITY OF RIO DE JANEIRO   (Brazil)

Author keywords

Leishmania; Peptidase inhibitors; Trypanosoma brucei; Trypanosoma cruzi

Indexed keywords

4 CHLOROMERCURIBENZOIC ACID; ANTIFUNGAL AGENT; ANTIPARASITIC AGENT; ANTITRYPANOSOMAL AGENT; BENZNIDAZOLE; CATHEPSIN L; CHALCONE DERIVATIVE; CRUZIPAIN; CYCLOHEXANE; CYSTEINE; CYSTEINE PEPTIDASE INHIBITOR; EFLORNITHINE; FALCIPAIN 2; HYDROXYLAMINE; IODOACETAMIDE; ISONIAZID; K 11002; K 11777; MELARSOPROL; METHYL CHLORIDE; NIFURTIMOX; PAROMOMYCIN; PENTAMIDINE; SINTAMAQUINE; SULFONAMIDE; THIOSEMICARBAZONE DERIVATIVE; THIOUREA; UNCLASSIFIED DRUG; UNINDEXED DRUG; VIRULENCE FACTOR; ZLIII 43A;

AFRICAN TRYPANOSOMIASIS; ARTICLE; BLOOD TRANSFUSION; CARDIOMYOPATHY; CHAGAS DISEASE; DIELS ALDER REACTION; EARLY DIAGNOSIS; EPIMASTIGOTE; HUMAN; HYPOGLYCEMIA; IC 50; IMMUNOELECTRON MICROSCOPY; KINETOPLASTIDA; LEISHMANIA; LEISHMANIASIS; MULTIGENE FAMILY; NEPHROTOXICITY; NONHUMAN; PARASITE TRANSMISSION; PARASITE VIRULENCE; PARASITEMIA; PARASITOSIS; PATHOGENESIS; PATIENT CARE; PROTOZOON; PUBLIC HEALTH; TRYPANOSOMA BRUCEI; TRYPANOSOMA CRUZI; VISCERAL LEISHMANIASIS;

CYSTEINE PROTEASES; HUMANS; PROTEASE INHIBITORS; PROTOZOAN PROTEINS; TRYPANOCIDAL AGENTS; TRYPANOSOMA; TRYPANOSOMIASIS;

EID: 84880303156     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/0929867311320250009     Document Type: Article

References (188)

1. Coura, J.R.; Borges-Pereira, J. Chagas disease. What is known and what should be improved: a systemic review. Rev. Soc. Bras. Med. Trop., 2012, 45(3), 286-296.
2. Coura, J.R. Present situation and new strategies for Chagas disease chemotherapy: a proposal. Mem. Inst. Oswaldo. Cruz., 2009, 104(4), 549-554.
3. Coura, J.R. Zigman Brener (7/9/1928 -23/9/2002). Mem. Inst. Oswaldo. Cruz, 2002, 97(7), 915-916.
4. Wilkinson, S.R.; Taylor, M.C.; Horn, D.; Kelly, J.M.; Cheeseman, I. A mechanism for cross-resistance to nifurtimox and benznidazole in trypanosomes. Proc. Natl. Acad. Sci. U S A, 2008, 105(13), 5022-5027.
5. Hall, B.S.; Bot, C.; Wilkinson, S.R. Nifurtimox activation by trypanosomal type I nitroreductases generates cytotoxic nitrile metabolites. J. Biol. Chem., 2011, 286(15), 13088-13095.
6. Docampo, R. Sensitivity of parasites to free radical damage by antiparasitic drugs. Chem. Biol. Interact., 1990, 73(1), 1-27.
7. Hall, B.S.; Wilkinson, S.R. Activation of benznidazole by trypanosomal type I nitroreductases results in glyoxal formation. Antimicrob. Agents. Chemother., 2012, 56(1), 115-123.
8. Mejia, A.M.; Hall, B.S.; Taylor, M.C.; Gomez-Palacio, A.; Wilkinson, S.R.; Triana-Chavez, O.; Kelly, J.M. Benznidazole-resistance in Trypanosoma cruzi is a readily acquired trait that can arise independently in a single population. J. Infect. Dis., 2012, 206(2), 220-228.
9. Kennedy, P.G. An alternative form of melarsoprol in sleeping sickness. Trends Parasitol., 2012, 28(8), 307-310.
10. Krafsur, E.S. Tsetse flies: genetics, evolution, and role as vectors. Infect. Genet. Evol., 2009, 9(1), 124-141.
11. Kennedy, P.G. The continuing problem of human African trypanosomiasis (sleeping sickness). Ann. Neurol., 2008, 64(2), 116-126.
12. Priotto, G.; Kasparian, S.; Mutombo, W.; Ngouama, D.; Ghorashian, S.; Arnold, U.; Ghabri, S.; Baudin, E.; Buard, V.; Kazadi-Kyanza, S.; Ilunga, M.; Mutangala, W.; Pohlig, G.; Schmid, C.; Karunakara, U.; Torreele, E.; Kande, V. Nifurtimoxeflornithine combination therapy for second-stage African Trypanosoma brucei gambiense trypanosomiasis: a multicentre, randomised, phase III, non-inferiority trial. Lancet, 2009, 374(9683), 56-64.
13. Simarro, P.P.; Diarra, A.; Ruiz Postigo, J.A.; Franco, J.R.; Jannin, J.G., The human African trypanosomiasis control and surveillance programme of the World Health Organization 2000-2009: the way forward. PLoS. Negl. Trop. Dis., 2011, 5(2), e1007.
14. Torreele, E.; Bourdin Trunz, B.; Tweats, D.; Kaiser, M.; Brun, R.; Mazue, G.; Bray, M.A.; Pecoul, B. Fexinidazole-a new oral nitroimidazole drug candidate entering clinical development for the treatment of sleeping sickness. PLoS. Negl. Trop. Dis., 2010, 4(12), e923.
15. Jacobs, R.T.; Nare, B.; Wring, S.A.; Orr, M.D.; Chen, D.; Sligar, J.M.; Jenks, M.X.; Noe, R.A.; Bowling, T.S.; Mercer, L.T.; Rewerts, C.; Gaukel, E.; Owens, J.; Parham, R.; Randolph, R.; Beaudet, B.; Bacchi, C.J.; Yarlett, N.; Plattner, J.J.; Freund, Y.; Ding, C.; Akama, T.; Zhang, Y.K.; Brun, R.; Kaiser, M.; Scandale, I.; Don, R. SCYX-7158, an orally-active benzoxaborole for the treatment of stage 2 human African trypanosomiasis. PLoS. Negl. Trop. Dis., 2011, 5(6), e1151.
16. Rodgers, J.; Jones, A.; Gibaud, S.; Bradley, B.; McCabe, C.; Barrett, M.P.; Gettinby, G.; Kennedy, P.G. Melarsoprol cyclodextrin inclusion complexes as promising oral candidates for the treatment of human African trypanosomiasis. PLoS. Negl. Trop. Dis., 2011, 5(9), e1308.
17. Ameen, M. Cutaneous leishmaniasis: advances in disease pathogenesis, diagnostics and therapeutics. Clin. Exp. Dermatol., 2010, 35(7), 699-705.
18. Amato, V.S.; Tuon, F.F.; Bacha, H.A.; Neto, V.A.; Nicodemo, A.C. Mucosal leishmaniasis. Current scenario and prospects for treatment. Acta Trop., 2008, 105(1), 1-9.
19. Kaye, P.M.; Aebischer, T. Visceral leishmaniasis: immunology and prospects for a vaccine. Clin. Microbiol. Infect., 2011, 17(10), 1462-1470.
20. Singh, R.K.; Pandey, H.P.; Sundar, S. Visceral leishmaniasis (kalaazar): challenges ahead. Indian J. Med. Res., 2006, 123(3), 331-344.
21. Sereno, D.; Holzmuller, P.; Mangot, I.; Cuny, G.; Ouaissi, A.; Lemesre, J.L. Antimonial-mediated DNA fragmentation in Leishmania infantum amastigotes. Antimicrob. Agents Chemother., 2001, 45(7), 2064-2069.
22. 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(38), 39925-39932.
23. Ephros, M.; Bitnun, A.; Shaked, P.; Waldman, E.; Zilberstein, D. Stage-specific activity of pentavalent antimony against Leishmania donovani axenic amastigotes. Antimicrob. Agents Chemother., 1999, 43(2), 278-282.
24. Torres, D.C.; Adaui, V.; Ribeiro-Alves, M.; Romero, G.A.; Arevalo, J.; Cupolillo, E.; Dujardin, J.C. Targeted gene expression profiling in Leishmania braziliensis and Leishmania guyanensis parasites isolated from Brazilian patients with different antimonial treatment outcomes. Infect. Genet. Evol., 2010, 10(6), 727-733.
25. Bern, C.; Adler-Moore, J.; Berenguer, J.; Boelaert, M.; den Boer, M.; Davidson, R.N.; Figueras, C.; Gradoni, L.; Kafetzis, D.A.; Ritmeijer, K.; Rosenthal, E.; Royce, C.; Russo, R.; Sundar, S.; Alvar, J. Liposomal amphotericin B for the treatment of visceral leishmaniasis. Clin. Infect. Dis., 2006, 43(7), 917-924.
26. Sundar, S.; Chatterjee, M. Visceral leishmaniasis -current therapeutic modalities. Indian J. Med. Res., 2006, 123(3), 345-352.
27. Mbongo, N.; Loiseau, P.M.; Billion, M.A.; Robert-Gero, M. Mechanism of amphotericin B resistance in Leishmania donovani promastigotes. Antimicrob. Agents Chemother., 1998, 42(2), 352-357.
28. Perez-Victoria, F.J.; Gamarro, F.; Ouellette, M.; Castanys, S. Functional cloning of the miltefosine transporter. A novel P-type phospholipid translocase from Leishmania involved in drug resistance. J. Biol. Chem., 2003, 278(50), 49965-49971.
29. Soto, J.; Buffet, P.; Grogl, M.; Berman, J. Successful treatment of Colombian cutaneous leishmaniasis with four injections of pentamidine. Am. J. Trop. Med. Hyg., 1994, 50(1), 107-111.
30. Das, V.N.; Ranjan, A.; Sinha, A.N.; Verma, N.; Lal, C.S.; Gupta, A.K.; Siddiqui, N.A.; Kar, S.K. A randomized clinical trial of low dosage combination of pentamidine and allopurinol in the treatment of antimony unresponsive cases of visceral leishmaniasis. J. Assoc. Physicians India, 2001, 49, 609-613.
31. Jha, T.K.; Sundar, S.; Thakur, C.P.; Felton, J.M.; Sabin, A.J.; Horton, J. A phase II dose-ranging study of sitamaquine for the treatment of visceral leishmaniasis in India. Am. J. Trop. Med. Hyg., 2005, 73(6), 1005-1011.
32. Bories, C.; Cojean, S.; Huteau, F.; Loiseau, P.M. Selection and phenotype characterisation of sitamaquine-resistant promastigotes of Leishmania donovani. Biomed. Pharmacother., 2008, 62(3), 164-167.
33. el-On, J.; Halevy, S.; Grunwald, M.H.; Weinrauch, L. Topical treatment of Old World cutaneous leishmaniasis caused by Leishmania major: a double-blind control study. J. Am. Acad. Dermatol., 1992, 27(2 Pt 1), 227-231.
34. Ben Salah, A.; Buffet, P.A.; Morizot, G.; Ben Massoud, N.; Zaatour, A.; Ben Alaya, N.; Haj Hamida, N.B.; El Ahmadi, Z.; Downs, M.T.; Smith, P.L.; Dellagi, K.; Grogl, M. WR279,396, a third generation aminoglycoside ointment for the treatment of Leishmania major cutaneous leishmaniasis: a phase 2, randomized, double blind, placebo controlled study. PLoS. Negl. Trop. Dis., 2009, 3(5), e432.
35. Itow, S.; Camargo, E.P. Proteolytic activites in cell extracts of Trypanosoma cruzi. J. Protozool., 1977, 24(4), 591-595.
36. Bongertz, V.; Hungerer, K.D. Trypanosoma cruzi: isolation and characterization of a protease. Exp. Parasitol., 1978, 45(1), 8-18.
37. Rangel, H.A.; Araujo, P.M.; Repka, D.; Costa, M.G. Trypanosoma cruzi: isolation and characterization of a proteinase. Exp. Parasitol,. 1981, 52(2), 199-209.
38. Cazzulo, J.J.; Couso, R.; Raimondi, A.; Wernstedt, C.; Hellman, U. Further characterization and partial amino acid sequence of a cysteine proteinase from Trypanosoma cruzi. Mol. Biochem. Parasitol., 1989, 33(1), 33-41.
39. Greig, S.; Ashall, F. Electrophoretic detection of Trypanosoma cruzi peptidases. Mol. Biochem. Parasitol., 1990, 39(1), 31-37.
40. Ashall, F. Characterisation of an alkaline peptidase of Trypanosoma cruzi and other trypanosomatids. Mol. Biochem. Parasitol., 1990, 38(1), 77-87.
41. Ashall, F.; Healy, N.; Greig, S.; Kiderlen, A.; Curry, A.; Blackwell, J. Detection of an alkaline peptidase in Leishmania amastigotes and promastigotes. Biochem. Soc. Trans., 1990, 18(5), 864-865.
42. Drake, L.J.; Healy, N.; Greig, S.; Ashall, F. Detection of peptidase activities in Trypanosoma cruzi using chromogenic and fluorogenic substrates. Biochem. Soc. Trans., 1990, 18(5), 865-866.
43. Roberts, H.; Healy, N.; Shaw, E.; Ashall, F. Substrate specificity and inhibitor sensitivity of a Trypanosoma cruzi alkaline peptidase. Biochem. Soc. Trans., 1990, 18(5), 866-867.
44. Campetella, O.; Martinez, J.; Cazzulo, J.J. A major cysteine proteinase is developmentally regulated in Trypanosoma cruzi. FEMS Microbiol. Lett., 1990, 55(1-2), 145-149.
45. Tomas, A.M.; Kelly, J.M. Stage-regulated expression of cruzipain, the major cysteine protease of Trypanosoma cruzi is independent of the level of RNA1. Mol. Biochem. Parasitol., 1996, 76(1-2), 91-103.
46. Piras, M.M.; Henriquez, D.; Piras, R. The effect of proteolytic enzymes and protease inhibitors on the interaction Trypanosoma cruzi-fibroblasts. Mol. Biochem. Parasitol., 1985, 14(2), 151-163.
47. Ashall, F.; Harris, D.; Roberts, H.; Healy, N.; Shaw, E. Substrate specificity and inhibitor sensitivity of a trypanosomatid alkaline peptidase. Biochim. Biophys. Acta, 1990, 1035(3), 293-299.
48. Cazzulo, J.J.; Hellman, U.; Couso, R.; Parodi, A.J. Amino acid and carbohydrate composition of a lysosomal cysteine proteinase from Trypanosoma cruzi. Absence of phosphorylated mannose residues. Mol. Biochem. Parasitol., 1990, 38(1), 41-48.
49. Cazzulo, J.J.; Cazzulo Franke, M.C.; Martinez, J.; Franke de Cazzulo, B.M. Some kinetic properties of a cysteine proteinase (cruzipain) from Trypanosoma cruzi. Biochim. Biophys. Acta, 1990, 1037(2), 186-191.
50. Scharfstein, J.; Rodrigues, M.M.; Alves, C.A.; de Souza, W.; Previato, J.O.; Mendonca-Previato, L. Trypanosoma cruzi: description of a highly purified surface antigen defined by human antibodies. J. Immunol., 1983, 131(2), 972-976.
51. Scharfstein, J.; Schechter, M.; Senna, M.; Peralta, J.M.; Mendonca-Previato, L.; Miles, M.A. Trypanosoma cruzi: characterization and isolation of a 57/51,000 m.w. surface glycoprotein (GP57/51) expressed by epimastigotes and bloodstream trypomastigotes. J. Immunol., 1986, 137(4), 1336-1341.
52. Murta, A.C.; Persechini, P.M.; Padron Tde, S.; de Souza, W.; Guimaraes, J.A.; Scharfstein, J. Structural and functional identification of GP57/51 antigen of Trypanosoma cruzi as a cysteine proteinase. Mol. Biochem. Parasitol., 1990, 43(1), 27-38.
53. Bonaldo, M.C.; Scharfstein, J.; Murta, A.C.; Goldenberg, S. Further characterization of Trypanosoma cruzi GP57/51 as the major antigen expressed by differentiating epimastigotes. Parasitol. Res., 1991, 77(7), 567-571.
54. Bontempi, E.; Martinez, J.; Cazzulo, J.J. Subcellular localization of a cysteine proteinase from Trypanosoma cruzi. Mol. Biochem. Parasitol., 1989, 33(1), 43-47.
55. Souto-Padron, T.; Campetella, O.E.; Cazzulo, J.J.; de Souza, W. Cysteine proteinase in Trypanosoma cruzi: immunocytochemical localization and involvement in parasite-host cell interaction. J. Cell. Sci., 1990, 96 (Pt 3), 485-490.
56. Eakin, A.E.; Mills, A.A.; Harth, G.; McKerrow, J.H.; Craik, C.S. The sequence, organization, and expression of the major cysteine protease (cruzain) from Trypanosoma cruzi. J. Biol. Chem., 1992, 267(11), 7411-7420.
57. Campetella, O.; Henriksson, J.; Aslund, L.; Frasch, A.C.; Pettersson, U.; Cazzulo, J.J. The major cysteine proteinase (cruzipain) from Trypanosoma cruzi is encoded by multiple polymorphic tandemly organized genes located on different chromosomes. Mol. Biochem. Parasitol., 1992, 50(2), 225-234.
58. Lima, A.P.; Tessier, D.C.; Thomas, D.Y.; Scharfstein, J.; Storer, A.C.; Vernet, T. Identification of new cysteine protease gene isoforms in Trypanosoma cruzi. Mol. Biochem. Parasitol., 1994, 67(2), 333-338.
59. Mottram, J.C.; North, M.J.; Barry, J.D.; Coombs, G.H. A cysteine proteinase cDNA from Trypanosoma brucei predicts an enzyme with an unusual C-terminal extension. FEBS Lett., 1989, 258(2), 211-215.
60. McGrath, M.E.; Eakin, A.E.; Engel, J.C.; McKerrow, J.H.; Craik, C.S.; Fletterick, R.J. The crystal structure of cruzain: a therapeutic target for Chagas' disease. J. Mol. Biol., 1995, 247(2), 251-259.
61. Caffrey, C.R.; Steverding, D. Kinetoplastid papain-like cysteine peptidases. Mol. Biochem. Parasitol., 2009, 167(1), 12-19.
62. Judice, W.A.; Cezari, M.H.; Lima, A.P.; Scharfstein, J.; Chagas, J.R.; Tersariol, I.L.; Juliano, M.A.; Juliano, L. Comparison of the specificity, stability and individual rate constants with respective activation parameters for the peptidase activity of cruzipain and its recombinant form, cruzain, from Trypanosoma cruzi. Eur. J. Biochem., 2001, 268(24), 6578-6586.
63. Hellman, U.; Wernstedt, C.; Cazzulo, J.J. Self-proteolysis of the cysteine proteinase, cruzipain, from Trypanosoma cruzi gives a major fragment corresponding to its carboxy-terminal domain. Mol. Biochem. Parasitol., 1991, 44(1), 15-21.
64. Scharfstein, J.; Luquetti, A.; Murta, A.C.; Senna, M.; Rezende, J.M.; Rassi, A.; Mendonca-Previato, L. Chagas' disease: serodiagnosis with purified Gp25 antigen. Am. J. Trop. Med. Hyg., 1985, 34(6), 1153-1160.
65. Cazzulo, J.J.; Martinez, J.; Parodi, A.J.; Wernstedt, C.; Hellman, U. On the post-translational modifications at the C-terminal domain of the major cysteine proteinase (cruzipain) from Trypanosoma cruzi. FEMS Microbiol. Lett., 1992, 79(1-3), 411-416.
66. Aslund, L.; Henriksson, J.; Campetella, O.; Frasch, A.C.; Pettersson, U.; Cazzulo, J.J. The C-terminal extension of the major cysteine proteinase (cruzipain) from Trypanosoma cruzi. Mol. Biochem. Parasitol., 1991, 45(2), 345-347.
67. Lima, A.P.; Scharfstein, J.; Storer, A.C.; Menard, R. Temperaturedependent substrate inhibition of the cysteine proteinase (GP57/51) from Trypanosoma cruzi. Mol. Biochem. Parasitol., 1992, 56(2), 335-338.
68. Gillmor, S.A.; Craik, C.S.; Fletterick, R.J. Structural determinants of specificity in the cysteine protease cruzain. Protein Sci., 1997, 6(8), 1603-1611.
69. Stoka, V.; McKerrow, J.H.; Cazzulo, J.J.; Turk, V. Substrate inhibition of cruzipain is not affected by the C-terminal domain. FEBS Lett., 1998, 429(2), 129-133.
70. Salvati, L.; Mattu, M.; Polticelli, F.; Tiberi, F.; Gradoni, L.; Venturini, G.; Bolognesi, M.; Ascenzi, P. Modulation of the catalytic activity of cruzipain, the major cysteine proteinase from Trypanosoma cruzi, by temperature and pH. Eur. J. Biochem., 2001, 268(11), 3253-3258.
71. Serveau, C.; Lalmanach, G.; Juliano, M.A.; Scharfstein, J.; Juliano, L.; Gauthier, F. Investigation of the substrate specificity of cruzipain, the major cysteine proteinase of Trypanosoma cruzi, through the use of cystatin-derived substrates and inhibitors. Biochem. J., 1996, 313 (Pt 3), 951-956.
72. Lalmanach, G.; Mayer, R.; Serveau, C.; Scharfstein, J.; Gauthier, F. Biotin-labelled peptidyl diazomethane inhibitors derived from the substrate-like sequence of cystatin: targeting of the active site of cruzipain, the major cysteine proteinase of Trypanosoma cruzi. Biochem. J., 1996, 318 (Pt 2), 395-399.
73. Nery, E.D.; Juliano, M.A.; Meldal, M.; Svendsen, I.; Scharfstein, J.; Walmsley, A.; Juliano, L. Characterization of the substrate specificity of the major cysteine protease (cruzipain) from Trypanosoma cruzi using a portion-mixing combinatorial library and fluorogenic peptides. Biochem. J., 1997, 323 (Pt 2), 427-433.
74. Del Nery, E.; Juliano, M.A.; Lima, A.P.; Scharfstein, J.; Juliano, L. Kininogenase activity by the major cysteinyl proteinase (cruzipain) from Trypanosoma cruzi. J. Biol. Chem., 1997, 272(41), 25713-25718.
75. Meldal, M.; Svendsen, I.B.; Juliano, L.; Juliano, M.A.; Nery, E.D.; Scharfstein, J. Inhibition of cruzipain visualized in a fluorescence quenched solid-phase inhibitor library assay. D-amino acid inhibitors for cruzipain, cathepsin B and cathepsin L. J. Pept. Sci., 1998, 4(2), 83-91.
76. Serveau, C.; Lalmanach, G.; Hirata, I.; Scharfstein, J.; Juliano, M.A.; Gauthier, F. Discrimination of cruzipain, the major cysteine proteinase of Trypanosoma cruzi, and mammalian cathepsins B and L, by a pH-inducible fluorogenic substrate of trypanosomal cysteine proteinases. Eur. J. Biochem., 1999, 259(1-2), 275-280.
77. Lima, A.P.; Almeida, P.C.; Tersariol, I.L.; Schmitz, V.; Schmaier, A.H.; Juliano, L.; Hirata, I.Y.; Muller-Esterl, W.; Chagas, J.R.; Scharfstein, J. Heparan sulfate modulates kinin release by Trypanosoma cruzi through the activity of cruzipain. J. Biol. Chem., 2002, 277(8), 5875-5881.
78. Lima, A.P.; dos Reis, F.C.; Serveau, C.; Lalmanach, G.; Juliano, L.; Menard, R.; Vernet, T.; Thomas, D.Y.; Storer, A.C.; Scharfstein, J. Cysteine protease isoforms from Trypanosoma cruzi, cruzipain 2 and cruzain, present different substrate preference and susceptibility to inhibitors. Mol. Biochem. Parasitol., 2001, 114(1), 41-52.
79. dos Reis, F.C.; Judice, W.A.; Juliano, M.A.; Juliano, L.; Scharfstein, J.; Lima, A.P. The substrate specificity of cruzipain 2, a cysteine protease isoform from Trypanosoma cruzi. FEMS Microbiol. Lett., 2006, 259(2), 215-220.
80. Ashall, F.; Angliker, H.; Shaw, E. Lysis of trypanosomes by peptidyl fluoromethyl ketones. Biochem. Biophys. Res. Commun., 1990, 170(2), 923-929.
81. Rockett, K.A.; Playfair, J.H.; Ashall, F.; Targett, G.A.; Angliker, H.; Shaw, E. Inhibition of intraerythrocytic development of Plasmodium falciparum by proteinase inhibitors. FEBS Lett., 1990, 259(2), 257-259.
82. de Araujo-Jorge, T.C.; Sampaio, E.P.; de Souza, W. Trypanosoma cruzi: inhibition of host cell uptake of infective bloodstream forms by alpha-2-macroglobulin. Z Parasitenkd, 1986, 72(3), 323-329.
83. Meirelles, M.N.; Juliano, L.; Carmona, E.; Silva, S.G.; Costa, E.M.; Murta, A.C.; Scharfstein, J. Inhibitors of the major cysteinyl proteinase (GP57/51) impair host cell invasion and arrest the intracellular development of Trypanosoma cruzi in vitro. Mol. Biochem. Parasitol., 1992, 52(2), 175-184.
84. Harth, G.; Andrews, N.; Mills, A.A.; Engel, J.C.; Smith, R.; McKerrow, J.H. Peptide-fluoromethyl ketones arrest intracellular replication and intercellular transmission of Trypanosoma cruzi. Mol. Biochem. Parasitol., 1993, 58(1), 17-24.
85. Franke de Cazzulo, B.M.; Martinez, J.; North, M.J.; Coombs, G.H.; Cazzulo, J.J. Effects of proteinase inhibitors on the growth and differentiation of Trypanosoma cruzi. FEMS Microbiol. Lett., 1994, 124(1), 81-86.
86. Engel, J.C.; Doyle, P.S.; Palmer, J.; Hsieh, I.; Bainton, D.F.; McKerrow, J.H. Cysteine protease inhibitors alter Golgi complex ultrastructure and function in Trypanosoma cruzi. J. Cell Sci., 1998, 111 (Pt 5), 597-606.
87. Engel, J.C.; Doyle, P.S.; Hsieh, I.; McKerrow, J.H. Cysteine protease inhibitors cure an experimental Trypanosoma cruzi infection. J. Exp. Med., 1998, 188(4), 725-734.
88. North, M.J.; Coombs, G.H.; Barry, J.D. A comparative study of the proteolytic enzymes of Trypanosoma brucei, T. equiperdum, T. evansi, T. vivax, Leishmania tarentolae and Crithidia fasciculata. Mol. Biochem. Parasitol., 1983, 9(2), 161-180.
89. Lonsdale-Eccles, J.D.; Mpimbaza, G.W. Thiol-dependent proteases of African trypanosomes. Analysis by electrophoresis in sodium dodecyl sulphate/polyacrylamide gels co-polymerized with fibrinogen. Eur. J. Biochem., 1986, 155(3), 469-473.
90. Mbawa, Z.R.; Gumm, I.D.; Fish, W.R.; Lonsdale-Eccles, J.D. Endopeptidase variations among different life-cycle stages of African trypanosomes. Eur. J. Biochem., 1991, 195(1), 183-190.
91. Caffrey, C.R.; Hansell, E.; Lucas, K.D.; Brinen, L.S.; Alvarez Hernandez, A.; Cheng, J.; Gwaltney, S.L., 2nd; Roush, W.R.; Stierhof, Y.D.; Bogyo, M.; Steverding, D.; McKerrow, J.H. Active site mapping, biochemical properties and subcellular localization of rhodesain, the major cysteine protease of Trypanosoma brucei rhodesiense. Mol. Biochem. Parasitol., 2001, 118(1), 61-73.
92. Lonsdale-Eccles, J.D.; Grab, D.J. Lysosomal and non-lysosomal peptidyl hydrolases of the bloodstream forms of Trypanosoma brucei brucei. Eur. J. Biochem., 1987, 169(3), 467-475.
93. Robertson, C.D.; North, M.J.; Lockwood, B.C.; Coombs, G.H. Analysis of the proteinases of Trypanosoma brucei. J. Gen. Microbiol., 1990, 136(5), 921-925.
94. Huet, G.; Richet, C.; Demeyer, D.; Bisiau, H.; Soudan, B.; Tetaert, D.; Han, K.K.; Degand, P. Characterization of different proteolytic activities in Trypanosoma brucei brucei. Biochim. Biophys. Acta, 1992, 1138(3), 213-221.
95. Troeberg, L.; Pike, R.N.; Morty, R.E.; Berry, R.K.; Coetzer, T.H.; Lonsdale-Eccles, J.D. Proteases from Trypanosoma brucei brucei. Purification, characterisation and interactions with host regulatory molecules. Eur. J. Biochem., 1996, 238(3), 728-736.
96. Gosalia, D.N.; Salisbury, C.M.; Ellman, J.A.; Diamond, S.L. High throughput substrate specificity profiling of serine and cysteine proteases using solution-phase fluorogenic peptide microarrays. Mol. Cell Proteomics, 2005, 4(5), 626-636.
97. Costa, T.F.; Reis, F.C.; Lima, A.P. Substrate inhibition and allosteric regulation by heparan sulfate of Trypanosoma brucei cathepsin L. Biochim. Biophys. Acta, 2012, 1824(3), 493-501.
98. Reis, F.C.; Costa, T.F.; Sulea, T.; Mezzetti, A.; Scharfstein, J.; Bromme, D.; Menard, R.; Lima, A.P. The propeptide of cruzipain-a potent selective inhibitor of the trypanosomal enzymes cruzipain and brucipain, and of the human enzyme cathepsin F. FEBS J., 2007, 274(5), 1224-1234.
99. Mackey, Z.B.; O'Brien, T.C.; Greenbaum, D.C.; Blank, R.B.; McKerrow, J.H. A cathepsin B-like protease is required for host protein degradation in Trypanosoma brucei. J. Biol. Chem., 2004, 279(46), 48426-48433.
100. O'Brien, T.C.; Mackey, Z.B.; Fetter, R.D.; Choe, Y.; O'Donoghue, A.J.; Zhou, M.; Craik, C.S.; Caffrey, C.R.; McKerrow, J.H. A parasite cysteine protease is key to host protein degradation and iron acquisition. J. Biol. Chem., 2008, 283(43), 28934-28943.
101. Abdulla, M.H.; O'Brien, T.; Mackey, Z.B.; Sajid, M.; Grab, D.J.; McKerrow, J.H. RNA interference of Trypanosoma brucei cathepsin B and L affects disease progression in a mouse model. PLoS Negl. Trop. Dis., 2008, 2(9), e298.
102. Nikolskaia, O.V.; de, A.L.A.P.; Kim, Y.V.; Lonsdale-Eccles, J.D.; Fukuma, T.; Scharfstein, J.; Grab, D.J. Blood-brain barrier traversal by African trypanosomes requires calcium signaling induced by parasite cysteine protease. J. Clin. Invest., 2006, 116(10), 2739-2747.
103. Grab, D.J.; Garcia-Garcia, J.C.; Nikolskaia, O.V.; Kim, Y.V.; Brown, A.; Pardo, C.A.; Zhang, Y.; Becker, K.G.; Wilson, B.A.; de, A.L.A.P.; Scharfstein, J.; Dumler, J.S. Protease activated recep tor signaling is required for African trypanosome traversal of human brain microvascular endothelial cells. PLoS Negl. Trop. Dis., 2009, 3(7), e479.
104. Steverding, D.; Sexton, D.W.; Wang, X.; Gehrke, S.S.; Wagner, G.K.; Caffrey, C.R. Trypanosoma brucei: chemical evidence that cathepsin L is essential for survival and a relevant drug target. Int. J. Parasitol., 2012, 42(5), 481-488.
105. North, M.J.; Mottram, J.C.; Coombs, G.H. Cysteine proteinases of parasitic protozoa. Parasitol. Today, 1990, 6(8), 270-275.
106. Robertson, C.D.; Coombs, G.H. Characterisation of three groups of cysteine proteinases in the amastigotes of Leishmania mexicana mexicana. Mol. Biochem. Parasitol., 1990, 42(2), 269-276.
107. Mottram, J.C.; Robertson, C.D.; Coombs, G.H.; Barry, J.D. A developmentally regulated cysteine proteinase gene of Leishmania mexicana. Mol. Microbiol., 1992, 6(14), 1925-1932.
108. Souza, A.E.; Waugh, S.; Coombs, G.H.; Mottram, J.C. Characterization of a multi-copy gene for a major stage-specific cysteine proteinase of Leishmania mexicana. FEBS Lett., 1992, 311(2), 124-127.
109. Traub-Cseko, Y.M.; Duboise, M.; Boukai, L.K.; McMahon-Pratt, D. Identification of two distinct cysteine proteinase genes of Leishmania pifanoi axenic amastigotes using the polymerase chain reaction. Mol. Biochem. Parasitol., 1993, 57(1), 101-115.
110. Sakanari, J.A.; Nadler, S.A.; Chan, V.J.; Engel, J.C.; Leptak, C.; Bouvier, J. Leishmania major: comparison of the cathepsin L-and B-like cysteine protease genes with those of other trypanosomatids. Exp. Parasitol., 1997, 85(1), 63-76.
111. Souza, A.E.; Bates, P.A.; Coombs, G.H.; Mottram, J.C. Null mutants for the lmcpa cysteine proteinase gene in Leishmania mexicana. Mol. Biochem. Parasitol., 1994, 63(2), 213-220.
112. Mottram, J.C.; Souza, A.E.; Hutchison, J.E.; Carter, R.; Frame, M.J.; Coombs, G.H. Evidence from disruption of the lmcpb gene array of Leishmania mexicana that cysteine proteinases are virulence factors. Proc. Natl. Acad. Sci. U S A, 1996, 93(12), 6008-6013.
113. Bart, G.; Frame, M.J.; Carter, R.; Coombs, G.H.; Mottram, J.C. Cathepsin B-like cysteine proteinase-deficient mutants of Leishmania mexicana. Mol. Biochem. Parasitol., 1997, 88(1-2), 53-61.
114. Sanderson, S.J.; Pollock, K.G.; Hilley, J.D.; Meldal, M.; Hilaire, P.S.; Juliano, M.A.; Juliano, L.; Mottram, J.C.; Coombs, G.H. Expression and characterization of a recombinant cysteine proteinase of Leishmania mexicana. Biochem. J., 2000, 347(Pt 2), 383-388.
115. St Hilaire, P.M.; Alves, L.C.; Sanderson, S.J.; Mottram, J.C.; Juliano, M.A.; Juliano, L.; Coombs, G.H.; Meldal, M. The substrate specificity of a recombinant cysteine protease from Leishmania mexicana: application of a combinatorial peptide library approach. Chembiochem, 2000, 1(2), 115-122.
116. Alves, L.C.; St Hilaire, P.M.; Meldal, M.; Sanderson, S.J.; Mottram, J.C.; Coombs, G.H.; Juliano, L.; Juliano, M.A. Identification of peptides inhibitory to recombinant cysteine proteinase, CPB, of Leishmania mexicana. Mol. Biochem. Parasitol., 2001, 114(1), 81-88.
117. Alexander, J.; Coombs, G.H.; Mottram, J.C. Leishmania mexicana cysteine proteinase-deficient mutants have attenuated virulence for mice and potentiate a Th1 response. J. Immunol., 1998, 161(12), 6794-6801.
118. Buxbaum, L.U.; Denise, H.; Coombs, G.H.; Alexander, J.; Mottram, J.C.; Scott, P. Cysteine protease B of Leishmania mexicana inhibits host Th1 responses and protective immunity. J. Immunol., 2003, 171(7), 3711-3717.
119. Pollock, K.G.; McNeil, K.S.; Mottram, J.C.; Lyons, R.E.; Brewer, J.M.; Scott, P.; Coombs, G.H.; Alexander, J. The Leishmania mexicana cysteine protease, CPB2.8, induces potent Th2 responses. J. Immunol., 2003, 170(4), 1746-1753.
120. Saravia, N.G.; Escorcia, B.; Osorio, Y.; Valderrama, L.; Brooks, D.; Arteaga, L.; Coombs, G.; Mottram, J.; Travi, B.L. Pathogenicity and protective immunogenicity of cysteine proteinase-deficient mutants of Leishmania mexicana in non-murine models. Vaccine, 2006, 24(19), 4247-4259.
121. Rosenthal, P.J.; Wollish, W.S.; Palmer, J.T.; Rasnick, D. Antimalarial effects of peptide inhibitors of a Plasmodium falciparum cysteine proteinase. J. Clin. Invest., 1991, 88(5), 1467-1472.
122. Rosenthal, P.J.; Lee, G.K.; Smith, R.E. Inhibition of a Plasmodium vinckei cysteine proteinase cures murine malaria. J. Clin. Invest., 1993, 91(3), 1052-1056.
123. Scory, S.; Caffrey, C.R.; Stierhof, Y.D.; Ruppel, A.; Steverding, D. Trypanosoma brucei: killing of bloodstream forms in vitro and in vivo by the cysteine proteinase inhibitor Z-phe-ala-CHN2. Exp. Parasitol., 1999, 91(4), 327-333.
124. Troeberg, L.; Morty, R.E.; Pike, R.N.; Lonsdale-Eccles, J.D.; Palmer, J.T.; McKerrow, J.H.; Coetzer, T.H. Cysteine proteinase inhibitors kill cultured bloodstream forms of Trypanosoma brucei brucei. Exp. Parasitol., 1999, 91(4), 349-355.
125. Roush, W.R.; Gonzalez, F.V.; McKerrow, J.H.; Hansell, E. Design and synthesis of dipeptidyl alpha',beta'-epoxy ketones, potent irreversible inhibitors of the cysteine protease cruzain. Bioorg. Med. Chem. Lett., 1998, 8(19), 2809-2812.
126. Hernandez, A.A.; Roush, W.R. Recent advances in the synthesis, design and selection of cysteine protease inhibitors. Curr. Opin. Chem. Biol., 2002, 6(4), 459-465.
127. Gonzalez, F.V.; Izquierdo, J.; Rodriguez, S.; McKerrow, J.H.; Hansell, E. Dipeptidyl-alpha,beta-epoxyesters as potent irreversible inhibitors of the cysteine proteases cruzain and rhodesain. Bioorg. Med. Chem. Lett., 2007, 17(24), 6697-6700.
128. Scheidt, K.A.; Roush, W.R.; McKerrow, J.H.; Selzer, P.M.; Hansell, E.; Rosenthal, P.J. Structure-based design, synthesis and evaluation of conformationally constrained cysteine protease inhibitors. Bioorg. Med. Chem., 1998, 6(12), 2477-2494.
129. St Hilaire, P.M.; Alves, L.C.; Herrera, F.; Renil, M.; Sanderson, S.J.; Mottram, J.C.; Coombs, G.H.; Juliano, M.A.; Juliano, L.; Arevalo, J.; Meldal, M. Solid-phase library synthesis, screening, and selection of tight-binding reduced peptide bond inhibitors of a recombinant Leishmania mexicana cysteine protease B. J. Med. Chem., 2002, 45(10), 1971-1982.
130. Billich, S.; Knoop, M.T.; Hansen, J.; Strop, P.; Sedlacek, J.; Mertz, R.; Moelling, K. Synthetic peptides as substrates and inhibitors of human immune deficiency virus-1 protease. J. Biol. Chem., 1988, 263(34), 17905-17908.
131. Graven, A.; St Hilaire, P.M.; Sanderson, S.J.; Mottram, J.C.; Coombs, G.H.; Meldal, M. Combinatorial library of peptide isosters based on Diels-Alder reactions: identification of novel inhibitors against a recombinant cysteine protease from Leishmania mexicana. J. Comb. Chem., 2001, 3(5), 441-452.
132. Tornoe, C.W.; Sanderson, S.J.; Mottram, J.C.; Coombs, G.H.; Meldal, M. Combinatorial library of peptidotriazoles: identification of [1,2,3]-triazole inhibitors against a recombinant Leishmania mexicana cysteine protease. J. Comb. Chem., 2004, 6(3), 312-324.
133. Palmer, J.T.; Rasnick, D.; Klaus, J.L.; Bromme, D. Vinyl sulfones as mechanism-based cysteine protease inhibitors. J. Med. Chem., 1995, 38(17), 3193-3196.
134. Rosenthal, P.J.; Olson, J.E.; Lee, G.K.; Palmer, J.T.; Klaus, J.L.; Rasnick, D. Antimalarial effects of vinyl sulfone cysteine proteinase inhibitors. Antimicrob. Agents Chemother., 1996, 40(7), 1600-1603.
135. Selzer, P.M.; Pingel, S.; Hsieh, I.; Ugele, B.; Chan, V.J.; Engel, J.C.; Bogyo, M.; Russell, D.G.; Sakanari, J.A.; McKerrow, J.H. Cysteine protease inhibitors as chemotherapy: lessons from a parasite target. Proc. Natl. Acad. Sci. U S A, 1999, 96(20), 11015-11022.
136. Roush, W.R.; Cheng, J.; Knapp-Reed, B.; Alvarez-Hernandez, A.; McKerrow, J.H.; Hansell, E.; Engel, J.C. Potent second generation vinyl sulfonamide inhibitors of the trypanosomal cysteine protease cruzain. Bioorg. Med. Chem. Lett., 2001, 11(20), 2759-2762.
137. Barr, S.C.; Warner, K.L.; Kornreic, B.G.; Piscitelli, J.; Wolfe, A.; Benet, L.; McKerrow, J.H. A cysteine protease inhibitor protects dogs from cardiac damage during infection by Trypanosoma cruzi. Antimicrob. Agents Chemother., 2005, 49(12), 5160-5161.
138. McKerrow, J.H.; Doyle, P.S.; Engel, J.C.; Podust, L.M.; Robertson, S.A.; Ferreira, R.; Saxton, T.; Arkin, M.; Kerr, I.D.; Brinen, L.S.; Craik, C.S. Two approaches to discovering and developing new drugs for Chagas disease. Mem. Inst. Oswaldo. Cruz, 2009, 104 Suppl 1, 263-269.
139. Bryant, C.; Kerr, I.D.; Debnath, M.; Ang, K.K.; Ratnam, J.; Ferreira, R.S.; Jaishankar, P.; Zhao, D.; Arkin, M.R.; McKerrow, J.H.; Brinen, L.S.; Renslo, A.R. Novel non-peptidic vinylsulfones targeting the S2 and S3 subsites of parasite cysteine proteases. Bioorg. Med. Chem. Lett., 2009, 19(21), 6218-6221.
140. Kerr, I.D.; Lee, J.H.; Farady, C.J.; Marion, R.; Rickert, M.; Sajid, M.; Pandey, K.C.; Caffrey, C.R.; Legac, J.; Hansell, E.; McKerrow, J.H.; Craik, C.S.; Rosenthal, P.J.; Brinen, L.S. Vinyl sulfones as antiparasitic agents and a structural basis for drug design. J. Biol. Chem., 2009, 284(38), 25697-25703.
141. Chen, M.; Christensen, S.B.; Blom, J.; Lemmich, E.; Nadelmann, L.; Fich, K.; Theander, T.G.; Kharazmi, A. Licochalcone A, a novel antiparasitic agent with potent activity against human pathogenic protozoan species of Leishmania. Antimicrob. Agents Chemother., 1993, 37(12), 2550-2556.
142. Chen, M.; Christensen, S.B.; Theander, T.G.; Kharazmi, A. Antileishmanial activity of licochalcone A in mice infected with Leishmania major and in hamsters infected with Leishmania donovani. Antimicrob. Agents Chemother., 1994, 38(6), 1339-1344.
143. Li, R.; Kenyon, G.L.; Cohen, F.E.; Chen, X.; Gong, B.; Dominguez, J.N.; Davidson, E.; Kurzban, G.; Miller, R.E.; Nuzum, E.O.; et al. In vitro antimalarial activity of chalcones and their derivatives. J. Med. Chem., 1995, 38(26), 5031-5037.
144. Troeberg, L.; Chen, X.; Flaherty, T.M.; Morty, R.E.; Cheng, M.; Hua, H.; Springer, C.; McKerrow, J.H.; Kenyon, G.L.; Lonsdale-Eccles, J.D.; Coetzer, T.H.; Cohen, F.E. Chalcone, acyl hydrazide, and related amides kill cultured Trypanosoma brucei brucei. Mol. Med., 2000, 6(8), 660-669.
145. Caffrey, C.R.; Schanz, M.; Nkemngu, N.J.; Brush, M.; Hansell, E.; Cohen, F.E.; Flaherty, T.M.; McKerrow, J.H.; Steverding, D. Screening of acyl hydrazide proteinase inhibitors for antiparasitic activity against Trypanosoma brucei. Int. J. Antimicrob. Agents, 2002, 19(3), 227-231.
146. Lam, P.Y.; Jadhav, P.K.; Eyermann, C.J.; Hodge, C.N.; Ru, Y.; Bacheler, L.T.; Meek, J.L.; Otto, M.J.; Rayner, M.M.; Wong, Y.N.; et al. Rational design of potent, bioavailable, nonpeptide cyclic ureas as HIV protease inhibitors. Science, 1994, 263(5145), 380-384.
147. Du, X.; Hansell, E.; Engel, J.C.; Caffrey, C.R.; Cohen, F.E.; McKerrow, J.H. Aryl ureas represent a new class of antitrypanosomal agents. Chem. Biol., 2000, 7(9), 733-742.
148. Du, X.; Guo, C.; Hansell, E.; Doyle, P.S.; Caffrey, C.R.; Holler, T.P.; McKerrow, J.H.; Cohen, F.E. Synthesis and structure-activity relationship study of potent trypanocidal thio semicarbazone inhibitors of the trypanosomal cysteine protease cruzain. J. Med. Chem., 2002, 45(13), 2695-2707.
149. Imam, S.A.; Varma, R.S. Isatin-3-anils as excystment and cysticidal agents against Schizopyrenus russelli. Experientia, 1975, 31(11), 1287-1288.
150. Varma, R.S.; Khan, I.A. Potential biologically active agents. X. Synthesis of 3-arylimino-2-indolinones, and their 1-methyl-and 1-morpholino/piperidinomethyl derivatives as excystment and cysticidal agents against Schizopyrenus russelli. Pol. J. Pharmacol. Pharm., 1977, 29(5), 549-554.
151. Chiyanzu, I.; Hansell, E.; Gut, J.; Rosenthal, P.J.; McKerrow, J.H.; Chibale, K. Synthesis and evaluation of isatins and thiosemicarbazone derivatives against cruzain, falcipain-2 and rhodesain. Bioorg. Med. Chem. Lett., 2003, 13(20), 3527-3530.
152. Shuttleworth, S.J.; Nasturica, D.; Gervais, C.; Siddiqui, M.A.; Rando, R.F.; Lee, N. Parallel synthesis of isatin-based serine protease inhibitors. Bioorg. Med. Chem. Lett., 2000, 10(22), 2501-2504.
153. Greenbaum, D.C.; Mackey, Z.; Hansell, E.; Doyle, P.; Gut, J.; Caffrey, C.R.; Lehrman, J.; Rosenthal, P.J.; McKerrow, J.H.; Chibale, K. Synthesis and structure-activity relationships of parasiticidal thiosemicarbazone cysteine protease inhibitors against Plasmodium falciparum, Trypanosoma brucei, and Trypanosoma cruzi. J. Med. Chem., 2004, 47(12), 3212-3219.
154. Mallari, J.P.; Shelat, A.; Kosinski, A.; Caffrey, C.R.; Connelly, M.; Zhu, F.; McKerrow, J.H.; Guy, R.K. Discovery of trypanocidal thiosemicarbazone inhibitors of rhodesain and TbcatB. Bioorg. Med. Chem. Lett., 2008, 18(9), 2883-2885.
155. Mallari, J.P.; Shelat, A.A.; Obrien, T.; Caffrey, C.R.; Kosinski, A.; Connelly, M.; Harbut, M.; Greenbaum, D.; McKerrow, J.H.; Guy, R.K. Development of potent purine-derived nitrile inhibitors of the trypanosomal protease TbcatB. J. Med. Chem., 2008, 51(3), 545-552.
156. Mallari, J.P.; Shelat, A.A.; Kosinski, A.; Caffrey, C.R.; Connelly, M.; Zhu, F.; McKerrow, J.H.; Guy, R.K. Structure-guided development of selective TbcatB inhibitors. J. Med. Chem., 2009, 52(20), 6489-6493.
157. Mott, B.T.; Ferreira, R.S.; Simeonov, A.; Jadhav, A.; Ang, K.K.; Leister, W.; Shen, M.; Silveira, J.T.; Doyle, P.S.; Arkin, M.R.; McKerrow, J.H.; Inglese, J.; Austin, C.P.; Thomas, C.J.; Shoichet, B.K.; Maloney, D.J. Identification and optimization of inhibitors of trypanosomal cysteine proteases: cruzain, rhodesain, and TbCatB. J. Med. Chem., 2010, 53(1), 52-60.
158. Martichonok, V.; Plouffe, C.; Storer, A.C.; Menard, R.; Jones, J.B. Aziridine analogs of [[trans-(epoxysuccinyl)-L-leucyl]amino]-4-guanidinobutane (E-64) as inhibitors of cysteine proteases. J. Med. Chem., 1995, 38(16), 3078-3085.
159. Schirmeister, T. Inhibition of cysteine proteases by peptides containing aziridine-2,3-dicarboxylic acid building blocks. Biopolymers, 1999, 51(1), 87-97.
160. Schirmeister, T.; Peric, M. Aziridinyl peptides as inhibitors of cysteine proteases: effect of a free carboxylic acid function on inhibition. Bioorg. Med. Chem., 2000, 8(6), 1281-1291.
161. Ponte-Sucre, A.; Vicik, R.; Schultheis, M.; Schirmeister, T.; Moll, H., Aziridine-2,3-dicarboxylates, peptidomimetic cysteine protease inhibitors with antileishmanial activity. Antimicrob. Agents Chemother., 2006, 50(7), 2439-2447.
162. Vicik, R.; Busemann, M.; Gelhaus, C.; Stiefl, N.; Scheiber, J.; Schmitz, W.; Schulz, F.; Mladenovic, M.; Engels, B.; Leippe, M.; Baumann, K.; Schirmeister, T. Aziridide-based inhibitors of cathepsin L: synthesis, inhibition activity, and docking studies. ChemMedChem, 2006, 1(10), 1126-1141.
163. Vicik, R.; Hoerr, V.; Glaser, M.; Schultheis, M.; Hansell, E.; McKerrow, J.H.; Holzgrabe, U.; Caffrey, C.R.; Ponte-Sucre, A.; Moll, H.; Stich, A.; Schirmeister, T. Aziridine-2,3-dicarboxylate inhibitors targeting the major cysteine protease of Trypanosoma brucei as lead trypanocidal agents. Bioorg. Med. Chem. Lett., 2006, 16(10), 2753-2757.
164. Setzer, W.N., Stokes, S.L., Penton, A.F., Takaku, S., Haber, W. A., Hansell, E., Caffrey, C.R., McKerrow, J.H. Cruzain inhibitory activity of leaf essential oils of neotropical Lauraceae and essential oil. Components. Nat. Prod. Commun., 2007, 2(12), 1203-1210.
165. Sean L. Stokes, R.A.C., Mariana P. Rangelova, William A. Haber; Setzer., a.W.N. Cruzain inhibitory activity of the leaf essential oil from an undescribed species of Eugenia from Monteverde, Costa Rica. Nat. Prod. Commun., 2007, 2(12), 1211-1213.
166. Lavrado, J.; Mackey, Z.; Hansell, E.; McKerrow, J.H.; Paulo, A.; Moreira, R. Antitrypanosomal and cysteine protease inhibitory activities of alkyldiamine cryptolepine derivatives. Bioorg. Med. Chem. Lett., 2012, 22(19), 6256-6260.
167. Lavrado, J.; Moreira, R.; Paulo, A. Indoloquinolines as scaffolds for drug discovery. Curr. Med. Chem., 2010, 17(22), 2348-2370.
168. Watts, K.R.; Ratnam, J.; Ang, K.H.; Tenney, K.; Compton, J.E.; McKerrow, J.; Crews, P. Assessing the trypanocidal potential of natural and semi-synthetic diketopiperazines from two deep water marine-derived fungi. Bioorg. Med. Chem., 2010, 18(7), 2566-2574.
169. Brak, K.; Doyle, P.S.; McKerrow, J.H.; Ellman, J.A. Identification of a new class of nonpeptidic inhibitors of cruzain. J. Am. Chem. Soc., 2008, 130(20), 6404-6410.
170. Brak, K.; Kerr, I.D.; Barrett, K.T.; Fuchi, N.; Debnath, M.; Ang, K.; Engel, J.C.; McKerrow, J.H.; Doyle, P.S.; Brinen, L.S.; Ellman, J.A. Nonpeptidic tetrafluorophenoxymethyl ketone cruzain inhibitors as promising new leads for Chagas disease chemotherapy. J. Med. Chem., 2010, 53(4), 1763-1773.
171. Monteiro, A.C.; Abrahamson, M.; Lima, A.P.; Vannier-Santos, M.A.; Scharfstein, J. Identification, characterization and localization of chagasin, a tight-binding cysteine protease inhibitor in Trypanosoma cruzi. J. Cell Sci., 2001, 114(Pt 21), 3933-3942.
172. Abrahamson, M.; Alvarez-Fernandez, M.; Nathanson, C.M. Cystatins. Biochem. Soc. Symp., 2003, 70, 179-199.
173. Sanderson, S.J.; Westrop, G.D.; Scharfstein, J.; Mottram, J.C.; Coombs, G.H. Functional conservation of a natural cysteine peptidase inhibitor in protozoan and bacterial pathogens. FEBS Lett., 2003, 542(1-3), 12-16.
174. Rigden, D.J.; Mosolov, V.V.; Galperin, M.Y. Sequence conservation in the chagasin family suggests a common trend in cysteine proteinase binding by unrelated protein inhibitors. Protein Sci., 2002, 11(8), 1971-1977.
175. Riekenberg, S.; Witjes, B.; Saric, M.; Bruchhaus, I.; Scholze, H. Identification of EhICP1, a chagasin-like cysteine protease inhibitor of Entamoeba histolytica. FEBS Lett., 2005, 579(7), 1573-1578.
176. Pandey, K.C.; Wang, S.X.; Sijwali, P.S.; Lau, A.L.; McKerrow, J.H.; Rosenthal, P.J. The Plasmodium falciparum cysteine protease falcipain-2 captures its substrate, hemoglobin, via a unique motif. Proc. Natl. Acad. Sci. U S A, 2005, 102(26), 9138-9143.
177. Santos, C.C.; Sant'anna, C.; Terres, A.; Cunha-e-Silva, N.L.; Scharfstein, J.; de, A.L.A.P. Chagasin, the endogenous cysteineprotease inhibitor of Trypanosoma cruzi, modulates parasite differentiation and invasion of mammalian cells. J. Cell Sci., 2005, 118(Pt 5), 901-915.
178. Rigden, D.J.; Monteiro, A.C.; Grossi de Sa, M.F. The protease inhibitor chagasin of Trypanosoma cruzi adopts an immunoglobulin-type fold and may have arisen by horizontal gene transfer. FEBS Lett., 2001, 504(1-2), 41-44.
179. Salmon, D.; do Aido-Machado, R.; Diehl, A.; Leidert, M.; Schmetzer, O.; de, A.L.A.P.; Scharfstein, J.; Oschkinat, H.; Pires, J.R. Solution structure and backbone dynamics of the Trypanosoma cruzi cysteine protease inhibitor chagasin. J. Mol. Biol., 2006, 357(5), 1511-1521.
180. Smith, B.O.; Picken, N.C.; Westrop, G.D.; Bromek, K.; Mottram, J.C.; Coombs, G.H. The structure of Leishmania mexicana ICP provides evidence for convergent evolution of cysteine peptidase inhibitors. J. Biol. Chem., 2006, 281(9), 5821-5828.
181. Figueiredo da Silva, A.A.; de Carvalho Vieira, L.; Krieger, M.A.; Goldenberg, S.; Zanchin, N.I.; Guimaraes, B.G. Crystal structure of chagasin, the endogenous cysteine-protease inhibitor from Trypanosoma cruzi. J. Struct. Biol., 2007, 157(2), 416-423.
182. Wang, S.X.; Pandey, K.C.; Scharfstein, J.; Whisstock, J.; Huang, R.K.; Jacobelli, J.; Fletterick, R.J.; Rosenthal, P.J.; Abrahamson, M.; Brinen, L.S.; Rossi, A.; Sali, A.; McKerrow, J.H. The structure of chagasin in complex with a cysteine protease clarifies the binding mode and evolution of an inhibitor family. Structure, 2007, 15(5), 535-543.
183. Ljunggren, A.; Redzynia, I.; Alvarez-Fernandez, M.; Abrahamson, M.; Mort, J.S.; Krupa, J.C.; Jaskolski, M.; Bujacz, G. Crystal structure of the parasite protease inhibitor chagasin in complex with a host target cysteine protease. J. Mol. Biol., 2007, 371(1), 137-153.
184. dos Reis, F.C.; Smith, B.O.; Santos, C.C.; Costa, T.F.; Scharfstein, J.; Coombs, G.H.; Mottram, J.C.; Lima, A.P. The role of conserved residues of chagasin in the inhibition of cysteine peptidases. FEBS Lett., 2008, 582(4), 485-490.
185. Uehara, L.A.; Moreira, O.C.; Oliveira, A.C.; Azambuja, P.; Lima, A.P.C.A.; Britto, C.; Santos, A.L.S.; Branquinha, M.; d'Avila-Levy, C.A. Cruzipain promotes Trypanosoma cruzi adhesion to Rhodnius prolixus midgut. PLoS Negl. Trop. Dis., 2012, 6(12): e1958.
186. Besteiro, S.; Coombs, G.H.; Mottram, J.C. A potential role for ICP, a Leishmanial inhibitor of cysteine peptidases, in the interaction between host and parasite. Mol. Microbiol., 2004, 54(5), 1224-1236.
187. Jecna, L.; Svarovska, A.; Besteiro, S.; Mottram, J.C.; Coombs, G.H.; Volf, P. Inhibitor of cysteine peptidase does not influence the development of Leishmania mexicana in Lutzomyia longipalpis. J. Med. Entomol., 2009, 46(3), 605-609.
188. Santos, C.C.; Coombs, G.H.; Lima, A.P.; Mottram, J.C. Role of the Trypanosoma brucei natural cysteine peptidase inhibitor ICP in differentiation and virulence. Mol. Microbiol., 2007, 66(4), 991-1002.