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Use of cysteine-reactive small molecules in drug discovery for trypanosomal disease

, PhD
Pages 353-366 | Published online: 06 Mar 2012

Bibliography

  • Nussbaum K, Honek J, Cadmus CM, Efferth T. Trypanosomatid parasites causing neglected diseases. Curr Med Chem 2010;17:1594-617
  • Ribeiro I, Sevcsik AM, Alves F, New, improved treatments for Chagas disease: from the R & D pipeline to the patients. PLoS Negl Trop Dis 2009;3:e484
  • Chappuis F, Sundar S, Hailu A, Visceral leishmaniasis: what are the needs for diagnosis, treatment and control? Nat Rev Microbiol 2007;5:873-82
  • Dujardin JC, Gonzalez-Pacanowska D, Croft SL, Collaborative actions in anti-trypanosomatid chemotherapy with partners from disease endemic areas. Trends Parasitol 2010;26:395-403
  • Wilkinson SR, Bot C, Kelly JM, Hall BS. Trypanocidal activity of nitroaromatic prodrugs: current treatments and future perspectives. Curr Top Med Chem 2011;11:2072-84
  • McKerrow JH, Doyle PS, Engel JC, Two approaches to discovering and developing new drugs for Chagas disease. Mem Inst Oswaldo Cruz 2009;104(Suppl 1):263-9
  • Alvarez VE, Niemirowicz GT, Cazzulo JJ. The peptidases of Trypanosoma cruzi: digestive enzymes, virulence factors, and mediators of autophagy and programmed cell death. Biochim Biophys Acta 2012;1824:195-205
  • Sajid M, McKerrow JH. Cysteine proteases of parasitic organisms. Mol Biochem Parasitol 2002;120:1-21
  • Urbina JA. Chemotherapy of Chagas disease. Curr Pharm Des 2002;8:287-95
  • Cazzulo JJ. Proteinases of Trypanosoma cruzi: potential targets for the chemotherapy of Chagas disease. Curr Top Med Chem 2002;2:1261-71
  • Lecaille F, Kaleta J, Bromme D. Human and parasitic papain-like cysteine proteases: their role in physiology and pathology and recent developments in inhibitor design. Chem Rev 2002;102:4459-88
  • Soeiro MN, de Castro SL. Trypanosoma cruzi targets for new chemotherapeutic approaches. Expert Opin Ther Targets 2009;13:105-21
  • Duschak VG, Couto AS. Cruzipain, the major cysteine protease of Trypanosoma cruzi: a sulfated glycoprotein antigen as relevant candidate for vaccine development and drug target. A review. Curr Med Chem 2009;16:3174-202
  • Sanchez-Sancho F, Campillo NE, Paez JA. Chagas disease: progress and new perspectives. Curr Med Chem 2010;17:423-52
  • Caffrey CR, Lima AP, Steverding D. Cysteine peptidases of kinetoplastid parasites. Adv Exp Med Biol 2011;712:84-99
  • Caffrey CR, Steverding D. Kinetoplastid papain-like cysteine peptidases. Mol Biochem Parasitol 2009;167:12-19
  • El Sayed NM, Myler PJ, Blandin G, Comparative genomics of trypanosomatid parasitic protozoa. Science 2005;309:404-9
  • Rivera G, Bocanegra-Garcia V, Ordaz-Pichardo C, New therapeutic targets for drug design against Trypanosoma cruzi, advances and perspectives. Curr Med Chem 2009;16:3286-93
  • Werbovetz KA. Target-based drug discovery for malaria, leishmaniasis, and trypanosomiasis. Curr Med Chem 2000;7:835-60
  • Moreira DR, Leite AC, dos Santos RR, Soares MB. Approaches for the development of new anti-Trypanosoma cruzi agents. Curr Drug Targets 2009;10:212-31
  • Black WC, Percival MD. The consequences of lysosomotropism on the design of selective cathepsin K inhibitors. ChemBioChem 2006;7:1525-35
  • Kometani M, Nonomura K, Tomoo T, Niwa S. Hurdles in the drug discovery of cathepsin K inhibitors. Curr Top Med Chem 2010;10:733-44
  • Zadeh-Vakili A, Taheri T, Taslimi Y, Immunization with the hybrid protein vaccine, consisting of Leishmania major cysteine proteinases Type I (CPB) and Type II (CPA), partially protects against leishmaniasis. Vaccine 2004;22:1930-40
  • Eakin AE, Mills AA, Harth G, The sequence, organization, and expression of the major cysteine protease (cruzain) from Trypanosoma cruzi. J Biol Chem 1992;267:7411-20
  • Alvarez V, Parussini F, Aslund L, Cazzulo JJ. Expression in insect cells of active mature cruzipain from Trypanosoma cruzi, containing its C-terminal domain. Protein Expr Purif 2002;26:467-75
  • Alves LC, Melo RL, Cezari MH, Analysis of the S(2) subsite specificities of the recombinant cysteine proteinases CPB of Leishmania mexicana, and cruzain of Trypanosoma cruzi, using fluorescent substrates containing non-natural basic amino acids. Mol Biochem Parasitol 2001;117:137-43
  • Judice WA, Cezari MH, Lima AP, 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;268:6578-86
  • Schurigt U, Schad C, Glowa C, Aziridine-2,3-dicarboxylate-based cysteine cathepsin inhibitors induce cell death in Leishmania major associated with accumulation of debris in autophagy-related lysosome-like vacuoles. Antimicrob Agents Chemother 2010;54:5028-41
  • Scory S, Stierhof YD, Caffrey CR, Steverding D. The cysteine proteinase inhibitor Z-Phe-Ala-CHN2 alters cell morphology and cell division activity of Trypanosoma brucei bloodstream forms in vivo. Kinetoplastid Biol Dis 2007;6:2
  • Nkemgu NJ, Grande R, Hansell E, Improved trypanocidal activities of cathepsin L inhibitors. Int J Antimicrob Agents 2003;22:155-9
  • Engel JC, Doyle PS, Palmer J, Cysteine protease inhibitors alter Golgi complex ultrastructure and function in Trypanosoma cruzi. J Cell Sci 1998;111(Pt 5):597-606
  • Meirelles MN, Juliano L, Carmona E, 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;52:175-84
  • Harth G, Andrews N, Mills AA, Peptide-fluoromethyl ketones arrest intracellular replication and intercellular transmission of Trypanosoma cruzi. Mol Biochem Parasitol 1993;58:17-24
  • Berasain P, Carmona C, Frangione B, Specific cleavage sites on human IgG subclasses by cruzipain, the major cysteine proteinase from Trypanosoma cruzi. Mol Biochem Parasitol 2003;130:23-9
  • Doyle PS, Zhou YM, Hsieh I, The Trypanosoma cruzi protease cruzain mediates immune evasion. PLoS Pathog 2011;7:e1002139
  • Santana JM, Grellier P, Schrevel J, Teixeira AR. A Trypanosoma cruzi-secreted 80 kDa proteinase with specificity for human collagen types I and IV. Biochem J 1997;325(Pt 1):129-37
  • Aparicio IM, Scharfstein J, Lima AP. A new cruzipain-mediated pathway of human cell invasion by Trypanosoma cruzi requires trypomastigote membranes. Infect Immun 2004;72:5892-902
  • Costales J, Rowland EC. A role for protease activity and host-cell permeability during the process of Trypanosoma cruzi egress from infected cells. J Parasitol 2007;93:1350-9
  • Schmitz V, Svensjo E, Serra RR, Proteolytic generation of kinins in tissues infected by Trypanosoma cruzi depends on CXC chemokine secretion by macrophages activated via Toll-like 2 receptors. J Leukoc Biol 2009;85:1005-14
  • Benitez-Hernandez I, Mendez-Enriquez E, Ostoa P, Proteolytic cleavage of chemokines by Trypanosoma cruzi's cruzipain inhibits chemokine functions by promoting the generation of antagonists. Immunobiology 2010;215:413-26
  • Mottram JC, Coombs GH, Alexander J. Cysteine peptidases as virulence factors of Leishmania. Curr Opin Microbiol 2004;7:375-81
  • Turk D, Turk B, Turk V. Papain-like lysosomal cysteine proteases and their inhibitors: drug discovery targets? Biochem Soc Symp 2003;(70):15-30
  • Garcia MP, Nobrega OT, Teixeira AR, Characterisation of a Trypanosoma cruzi acidic 30 kDa cysteine protease. Mol Biochem Parasitol 1998;91:263-72
  • Huang L, Lee A, Ellman JA. Identification of potent and selective mechanism-based inhibitors of the cysteine protease cruzain using solid-phase parallel synthesis. J Med Chem 2002;45:676-84
  • Machon U, Buchold C, Stempka M, On-bead screening of a combinatorial fumaric acid derived peptide library yields antiplasmodial cysteine protease inhibitors with unusual peptide sequences. J Med Chem 2009;52:5662-72
  • Baillie TA, Kassahun K. Reversibility in glutathione-conjugate formation. Adv Pharmacol 1994;27:163-81
  • Brak K, Kerr ID, Barrett KT, Nonpeptidic tetrafluorophenoxymethyl ketone cruzain inhibitors as promising new leads for Chagas disease chemotherapy. J Med Chem 2010;53:1763-73
  • Choe Y, Brinen LS, Price MS, Development of alpha-keto-based inhibitors of cruzain, a cysteine protease implicated in Chagas disease. Bioorg Med Chem 2005;13:2141-56
  • Beaulieu C, Isabel E, Fortier A, Identification of potent and reversible cruzipain inhibitors for the treatment of Chagas disease. Bioorg Med Chem Lett 2010;20:7444-9
  • Alves LC, Melo RL, Sanderson SJ, S1 subsite specificity of a recombinant cysteine proteinase, CPB, of Leishmania mexicana compared with cruzain, human cathepsin L and papain using substrates containing non-natural basic amino acids. Eur J Biochem 2001;268:1206-12
  • Bryant C, Kerr ID, Debnath M, Novel non-peptidic vinylsulfones targeting the S2 and S3 subsites of parasite cysteine proteases. Bioorg Med Chem Lett 2009;19:6218-21
  • Lecaille F, Authie E, Moreau T, Subsite specificity of trypanosomal cathepsin L-like cysteine proteases. Probing the S2 pocket with phenylalanine-derived amino acids. Eur J Biochem 2001;268:2733-41
  • Desmarais S, Black WC, Oballa R, Effect of cathepsin k inhibitor basicity on in vivo off-target activities. Mol Pharmacol 2008;73:147-56
  • Falgueyret JP, Desmarais S, Oballa R, Lysosomotropism of basic cathepsin K inhibitors contributes to increased cellular potencies against off-target cathepsins and reduced functional selectivity. J Med Chem 2005;48:7535-43
  • Stoch SA, Zajic S, Stone J, Effect of the cathepsin K inhibitor odanacatib on bone resorption biomarkers in healthy postmenopausal women: two double-blind, randomized, placebo-controlled phase I studies. Clin Pharmacol Ther 2009;86:175-82
  • McKerrow JH. Development of cysteine protease inhibitors as chemotherapy for parasitic diseases: insights on safety, target validation, and mechanism of action. Int J Parasitol 1999;29:833-7
  • Engel JC, Doyle PS, Hsieh I, McKerrow JH. Cysteine protease inhibitors cure an experimental Trypanosoma cruzi infection. J Exp Med 1998;188:725-34
  • Doyle PS, Zhou YM, Engel JC, McKerrow JH. A cysteine protease inhibitor cures Chagas' disease in an immunodeficient-mouse model of infection. Antimicrob Agents Chemother 2007;51:3932-9
  • Barr SC, Warner KL, Kornreic BG, A cysteine protease inhibitor protects dogs from cardiac damage during infection by Trypanosoma cruzi. Antimicrob Agents Chemother 2005;49:5160-1
  • Steert K, Berg M, Mottram JC, Alpha-ketoheterocycles as inhibitors of Leishmania mexicana cysteine protease CPB. ChemMedChem 2010;5:1734-48
  • Oballa RM, Truchon JF, Bayly CI, A generally applicable method for assessing the electrophilicity and reactivity of diverse nitrile-containing compounds. Bioorg Med Chem Lett 2007;17:998-1002
  • Gauthier JY, Chauret N, Cromlish W, The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K. Bioorg Med Chem Lett 2008;18:923-8
  • Isabel E, Bateman KP, Chauret N, The discovery of MK-0674, an orally bioavailable cathepsin K inhibitor. Bioorg Med Chem Lett 2010;20:887-92
  • Boyd MJ, Crane SN, Robichaud J, Investigation of ketone warheads as alternatives to the nitrile for preparation of potent and selective cathepsin K inhibitors. Bioorg Med Chem Lett 2009;19:675-9
  • Greenbaum DC, Mackey Z, Hansell E, Synthesis and structure-activity relationships of parasiticidal thiosemicarbazone cysteine protease inhibitors against Plasmodium falciparum, Trypanosoma brucei, and Trypanosoma cruzi. J Med Chem 2004;47:3212-19
  • Kassahun K, Black WC, Nicoll-Griffith D, Pharmacokinetics and metabolism in rats, dogs, and monkeys of the cathepsin k inhibitor odanacatib: demethylation of a methylsulfonyl moiety as a major metabolic pathway. Drug Metab Dispos 2011;39:1079-87
  • Higuchi MD. Endomyocardial biopsy in Chagas' heart disease: pathogenetic contributions. Sao Paulo Med J 1995;113:821-5
  • Mary C, Faraut F, Deniau M, Frequency of drug resistance gene amplification in clinical Leishmania strains. Int J Microbiol 2010: Article ID 819060, 8 pages
  • Zhang Y, Guo X, Lin ET, Benet LZ. Overlapping substrate specificities of cytochrome P450 3A and P-glycoprotein for a novel cysteine protease inhibitor. Drug Metab Dispos 1998;26:360-6
  • Mahar Doan KM, Humphreys JE, Webster LO, Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther 2002;303:1029-37
  • Hall BS, Wilkinson SR. Activation of benznidazole by trypanosomal type 1 nitroreductases results in glyoxal formation. Antimicrob Agents Chemother 2012;56:115-23
  • Hall BS, Bot C, Wilkinson SR. Nifurtimox activation by trypanosomal type 1 nitroreductases generates cytotoxic nitrile metabolites. J Biol Chem 2011;286:13088-95
  • Merlino A, Benitez D, Chavez S, Development of second generation amidinohydrazones, thio- and semicarbazones as Trypanosoma cruzi-inhibitors bearing benzofuroxan and benzimidazole 1,3-dioxane core scaffolds. Med Chem Commun 2010;1:216-28
  • Borst P, Ouellette M. New mechanisms of drug resistance in parasitic protozoa. Annu Rev Microbiol 1995;49:427-60
  • Maser P, Luscher A, Kaminsky R. Drug transport and drug resistance in African trypanosomes. Drug Resist Updat 2003;6:281-90
  • Haldar AK, Yadav V, Singhal E, Leishmania donovani isolates with antimony-resistant but not -sensitive phenotype inhibit sodium antimony gluconate-induced dendritic cell activation. PLoS Pathog 2010;6:e1000907
  • Wilkinson SR, Taylor MC, Horn D, A mechanism for cross-resistance to nifurtimox and benznidazole in trypanosomes. Proc Natl Acad Sci USA 2008;105:5022-7
  • Lima AP, dos Reis FC, Serveau C, Cysteine protease isoforms from Trypanosoma cruzi, cruzipain 2 and cruzain, present different substrate preference and susceptibility to inhibitors. Mol Biochem Parasitol 2001;114:41-52
  • Yong V, Schmitz V, Vannier-Santos MA, Altered expression of cruzipain and a cathepsin B-like target in a Trypanosoma cruzi cell line displaying resistance to synthetic inhibitors of cysteine-proteinases. Mol Biochem Parasitol 2000;109:47-59
  • Engel JC, Torres C, Hsieh I, Upregulation of the secretory pathway in cysteine protease inhibitor-resistant Trypanosoma cruzi. J Cell Sci 2000;113(Pt 8):1345-54
  • Murta SM, dos Santos WG, Anacleto C, Drug resistance in Trypanosoma cruzi is not associated with amplification or overexpression of P-glycoprotein (PGP) genes. Mol Biochem Parasitol 2001;117:223-8
  • Ouellette M, Borst P. Drug resistance and P-glycoprotein gene amplification in the protozoan parasite Leishmania. Res Microbiol 1991;142:737-46
  • Bustamante JM, Park HJ, Tarleton RL; and Chagas Drug Discovery Consortium. Report of the 2nd Chagas Drug Discovery Consortium meeting, held on 3 November 2010. 6 edition. Expert opin Drug Discover. Atlanta GA, USA: 2011;6:965-73
  • Jacobs RT, Nare B, Wring SA, SCYX-7158, an orally-active benzoxaborole for the treatment of stage 2 human African trypanosomiasis. PLoS Negl Trop Dis 2011;5:e1151
  • Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM269221.pdfhttp://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM269221.pdfhttp://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM269221.pdf
  • Pandey KC, Barkan DT, Sali A, Rosenthal PJ. Regulatory elements within the prodomain of Falcipain-2, a cysteine protease of the malaria parasite plasmodium falciparum. PLoS One 2009;4:e5694
  • Rosenthal PJ. Cysteine proteases of malaria parasites. Int J Parasitol 2004;34:1489-99
  • Brady CP, Brinkworth RI, Dalton JP, Molecular modeling and substrate specificity of discrete cruzipain-like and cathepsin L-like cysteine proteinases of the human blood fluke Schistosoma mansoni. Arch Biochem Biophys 2000;380:46-55
  • DuBois KN, Abodeely M, Sakanari J, Identification of the major cysteine protease of Giardia and its role in encystation. J Biol Chem 2008;283:18024-31
  • Kniel KE, Sumner SS, Pierson MD, Effect of hydrogen peroxide and other protease inhibitors on Cryptosporidium parvum excystation and in vitro development. J Parasitol 2004;90:885-8
  • Stanley SL. Pathophysiology of amoebiasis. Trends Parasitol 2001;17:280-5
  • Que X, Reed SL. Cysteine proteinases and the pathogenesis of amebiasis. Clin Microbiol Rev 2000;13:196-206
  • Kim K. Role of proteases in host cell invasion by Toxoplasma gondii and other Apicomplexa. Acta Trop 2004;91:69-81
  • Janoir C, Pechine S, Grosdidier C, Collignon A. Cwp84, a surface-associated protein of Clostridium difficile, is a cysteine protease with degrading activity on extracellular matrix proteins. J Bacteriol 2007;189:7174-80
  • Fujii N, Mallari JP, Hansell EJ, Discovery of potent thiosemicarbazone inhibitors of rhodesain and cruzain. Bioorg Med Chem Lett 2005;15:121-3
  • Bustamante JM, Tarleton RL. Methodological advances in drug discovery for Chagas disease. Expert Opin Drug Discov 2011;6:653-61
  • Mehta SR, Huang R, Yang M, Real-time in vivo green fluorescent protein imaging of a murine leishmaniasis model as a new tool for Leishmania vaccine and drug discovery. Clin Vaccine Immunol 2008;15:1764-70
  • Ndao M, Kelly N, Normandin D, Trypanosoma cruzi infection of squirrel monkeys: comparison of blood smear examination, commercial enzyme-linked immunosorbent assay, and polymerase chain reaction analysis as screening tests for evaluation of monkey-related injuries. Comp Med 2000;50:658-65
  • Laucella SA, Mazliah DP, Bertocchi G, Changes in Trypanosoma cruzi-specific immune responses after treatment: surrogate markers of treatment efficacy. Clin Infect Dis 2009;49:1675-84
  • Bustamante JM, Bixby LM, Tarleton RL. Drug-induced cure drives conversion to a stable and protective CD8+ T central memory response in chronic Chagas disease. Nat Med 2008;14:542-50
  • Turk V, Stoka V, Vasiljeva O, Cysteine cathepsins: from structure, function and regulation to new frontiers. Biochim Biophys Acta 2012;1824:68-88
  • Black WC, Bayly CI, Davis DE, Trifluoroethylamines as amide isosteres in inhibitors of cathepsin K. Bioorg Med Chem Lett 2005;15:4741-4

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