Aspartic peptidases of human pathogenic trypanosomatids: Perspectives and trends for chemotherapy

Current Medicinal Chemistry

Volumn 20, Issue 25, 2013, Pages 3116-3133

  Santos, L O ^a   Garcia Gomes, A S ^a,b   Catanho, M ^a   Sodre, C L ^c   Santos, A L S ^c   Branquinha, M H ^c   D'Avila Levy, C M ^a  

^a INSTITUTO OSWALDO CRUZ   (Brazil)

^b INSTITUTO FEDERAL DE EDUCAÇÃO   (Brazil)

^c FEDERAL UNIVERSITY OF RIO DE JANEIRO   (Brazil)

Author keywords

Alternative chemotherapy; Aspartic peptidases; Chagas' disease; HAART; HIV; HIV peptidase inhibitors; Leishmania; Leishmaniasis; Pathogenesis; Peptidases; Proteolytic inhibitors; Trypanosoma; Virulence

Indexed keywords

AMPRENAVIR; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; ANTIPROTOZOAL AGENT; ASPARTIC PEPTIDASE; CHLOROQUINE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ELASTASE INHIBITOR; INDINAVIR; LOPINAVIR; MEFLOQUINE; NELFINAVIR; PEPSTATIN; PEPTIDASE; PROTOZOAL PROTEIN; RITONAVIR; SAQUINAVIR; STIBOGLUCONATE SODIUM; THROMBIN INHIBITOR; UNCLASSIFIED DRUG;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; AMINO ACID SEQUENCE; ANTIMICROBIAL THERAPY; ANTIPROTOZOAL ACTIVITY; ARTICLE; CEREBROVASCULAR ACCIDENT; DRUG TARGETING; ENZYME ACTIVITY; ENZYME INHIBITION; GROWTH INHIBITION; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HYPERTENSION; IC 50; KINETOPLASTIDA; LEISHMANIA; LEISHMANIA BRAZILIENSIS; LEISHMANIA DONOVANI; LEISHMANIASIS; NONHUMAN; PROTEIN LOCALIZATION; SACCHAROMYCES CEREVISIAE; SYSTEMIC INFLAMMATORY RESPONSE SYNDROME; TRYPANOSOMA BRUCEI; TRYPANOSOMA CRUZI; TRYPANOSOMATID INFECTION;

ASPARTIC ACID PROTEASES; HIV PROTEASE INHIBITORS; HUMANS; NELFINAVIR; PROTOZOAN PROTEINS; SAQUINAVIR; TRYPANOCIDAL AGENTS; TRYPANOSOMA; TRYPANOSOMIASIS;

EID: 84880251936     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/0929867311320250007     Document Type: Article

References (125)

1. Wallace, F.G. The trypanosomatid parasites of insects and arachnids. Exp. Parasitol., 1966, 18, 124-193.
2. Mcghee, R.B.; Cosgrove, W.B. Biology and physiology of the lower Trypanosomatidae. Microbiol. Rev., 1980, 44, 140-173.
3. Vickerman, K. The evolutionary expansion of the trypanosomatid flagellates. Int. J. Parasitol., 1994, 24, 1317-1331.
4. De Souza, W.; Attias, M. In: Structures and organelles in pathogenic protists; Microbiology Monographs, Ed.; Springer: Berlin, 2010; Vol. 17, pp. 28-30.
5. Hoare, C.A.; Wallace, F.G. Developmental stages of trypanosomatid flagellates: a new terminology. Nature, 1966, 212, 1385-1386.
6. Svobodová, M.; Zídková, L.; Cepicka, I.; Oborník, M.; Lukes, J.; Vot-pka, J. Sergeia podlipaevi gen. nov., sp. nov. (Trypanosomatidae, Kinetoplastida), a parasite of biting midges (Ceratopogonidae, Diptera). Int. J. Syst. Evol. Microbiol., 2007, 57, 423-432.
7. Barret, M.P.; Curchmore, J.S.; Stich, A.; Lazzari, J.O.; Frasch, A.C.; Cazzulo, J.J.; Krishna, S. The trypanosomiases. The Lancet, 2003, 362, 1469-1480.
8. Stuart, K.; Brun, R.; Croft, S.; Fairlamb, A.; Gürtler, R.E.; McKerrow, J.; Reed, S.; Tarleton, R. Kinetoplastids: related protozoan pathogens, different diseases. J. Clin. Invest., 2008, 118, 1301-1310.
9. Bates, P.A. Leishmania sandfly interaction: progress and challenges. Curr. Opin. Microbiol., 2008, 11, 340-344.
10. Bates, P.A.; Rogers, M.E. New insights into the developmental biology and transmission mechanisms of Leishmania. Curr. Mol. Med., 2004, 4, 601-609.
11. Coura, J.R.; Borges-Pereira, J. Chagas disease: 100 years after its discovery. A systemic review. Acta Trop., 2010, 115, 5-13.
12. Welburn, S.C.; Maudlin, I. Tsetse-trypanosome interactions: rites of passage. Parasitol. Today, 1999, 15, 399-403.
13. World Health Organization. Control of the leishmaniasis. World Health Organ. Tech. Rep. Ser., 2010, 949, xii-xiii, 1-186, back cover.
14. Cavali, A.; Bolognesi, L. Neglected tropical diseases: multi-targetdirected ligands in the search for novel lead candidates against Trypanosoma and Leishmania. J. Glob. Infect. Dis., 2010, 2, 167-176.
15. Chakravarty, J.; Sundar, S. Drug resistance in leishmaniasis. J. Glob. Infect. Dis., 2010, 2, 167-176.
16. Bhandari, V.; Kulshrestha, A.; Deep, D.K.; Stark, O.; Prajapati, V.K.; Ramesh, V.; Sundar, S.; Schonian, G.; Dujardin, J.C.; Salotra, P. Drug susceptibility in Leishmania isolates following miltefosine treatment in cases of visceral leishmaniasis and post kala-azar dermal leishmaniasis. PLoS. Negl. Trop. Dis., 2012, 6, e1657.
17. Barrett, A.J. Classification of peptidases. Meth. Enzymol., 1994, 244, 1-15.
18. Beynon, R.J.; Bond, J.S. Proteolytic Enzymes: A Practical Approach, 2nd ed.; Oxford University Press: London, 2001.
19. Rawlings, N.D.; Barret, A.J.; Baterman, A. MEROPS: the database of proteolytic enzymes, their substrates and inhibitors. Nucleic Acids Res., 2012, 40, D343-350.
20. Barrett, A.J. In: Proteolysis in Cell Functions; Hopsu-Havu, V.K., Ed.; IOS Press: Amsterdam, 1997; Vol. 13, pp. 3-8.
21. Barret, A.J.; Rawlings, N.D.; O'Brien, E.A. The MEROPS database as a peptidase information system. J. Struct. Biol., 2001, 134, 95-102.
22. Barret, A.J.; Tolle, D.P.; Rwalings, N.D. Managing peptidases in the genomic era. Biol. Chem., 2003, 384, 873-882.
23. Lopez-Otín, C.; Bond, J.S. Proteases: multifunctional enzymes in life and disease. J. Biol. Chem., 2008, 283, 30433-30437.
24. Vermelho, A.B.; Melo, A.C.N.; Branquinha, M.H.S.; Santos, A.L.S.; d'Ávila-Levy, C.M.; Couri, S.; Bom, E.P.S. In: Enzimas em Biotecnologia-Produção, Aplicações e Mercado; Interciência: Rio de Janeiro, 2008; Vol. 1, pp. 273-287.
25. Hill, J.; Phylip, L. Bacterial aspartic proteinases. FEBS Lett., 1997, 409, 357-360.
26. James, M. In: Structure and Function of Aspartic Protease: Retroviral and Cellular Enzymes, Plenum Press: New York, 1998; Vol. 436, pp. 1-481.
27. Dash, C.; Kulkarni, A.; Dunn, B.; Rao, M. Aspartic peptidase inhibitors: implications in drug development. Crit. Rev. Biochem. Mol. Biol., 2003, 38, 89-119.
28. Horimoto, Y.; Dee, D.R.; Yada, R.Y. Multifunctional aspartic peptidase prosegments. New Biotechnol., 2009, 25, 318-324.
29. Cooper, J.B. Aspartic proteinases in disease: a structural perspective. Curr. Drug Targets, 2002, 3, 155-173.
30. Scott B.B.; McGeehan, G.M.; Harrison, R.K. Development of inhibitors of the aspartic protease renin for the treatment of hypertension. Curr. Protein Pept. Sci., 2006, 7, 241-254.
31. Coombs, G.H.; Goldberg, D.E.; Klemba, M.; Berry, C.; Kay, J.; Mottram, J.C. Aspartic proteases of Plasmodium falciparum and other parasitic protozoa as drug targets. Trends Parasitol., 2001, 17, 532-537.
32. Benes, P.; Vetvicka, V.; Funsek, M. Cathepsin D -many functions of aspartic protease. Crit. Rev. Oncol. Hematol., 2008, 68, 12-28.
33. Vassar, R. Beta-Secretase (BACE) as a drug target for Alzheimer's disease. Adv. Drug Deliv. Rev., 2002, 54, 1589-1602.
34. Dominguez, D.I.; Hartmann, D.; De Strooper, B. BACE1 and presenilin: two unusual aspartic proteases involved in Alzheimer's disease. Neurodegener. Dis., 2004, 1, 168-174.
35. James, M.N.; Sielecki, A.; Salituro, F.; Rich, D.H.; Hofmann, T. Conformational flexibility in the active sites of aspartic proteinases revealed by a pepstatin fragment binding to penicillopepsin. Proc. Natl. Acad. Sci., 1982, 79, 6137-6141.
36. Hyland, L.J.; Tomaszek, T.A.; Meek, T.D. Human immunodeficiency virus-1 protease 2. Use of pH rate studies and solvent kinetic isotope effects to elucidate details of chemical mechanism. Biochemistry, 1991, 30, 8454-8463.
37. Tossi, A.; Bonin, I.; Antcheva, N.; Norbedo, S.; Benedetti, F.; Miertus, S.; Nair, A.C.; Maliar, T.; Dal Bello, F.; Palù, G.; Romeo, D. Aspartic protease inhibitors. An integrated approach for the design and synthesis of diaminodiol based peptidomimetics. Eur. J. Biochem., 2000, 267, 1715-1722.
38. Davies, D.R. The structure and function of the aspartic proteinases. Annu. Rev. Biophys. Chem., 1990, 19, 189-215.
39. Blundell, T.L.; Johnson, M.S. Catching a common fold. Protein Sci., 1993, 2, 877-883.
40. Coates, L.; Erskine, P.T.; Mall, S.; Gill, R.; Wood, S.P.; Myles, D.A.; Cooper, J.B. X-ray, neutron and NMR studies of the catalytic mechanism of aspartic proteinases. Eur. Biophys. J., 2006, 35, 559-566.
41. Koelsch, G.; Mares, M.; Metcalf, P.; Fusek, M. Multiple functions of pro-parts of aspartic proteinase zymogens. FEBS Lett., 1994, 343, 6-10.
42. Foltmann, B. Structure and function of proparts in zymogens for aspartic proteinases. Biol. Chem. Hoppe-Seyler., 1988, 369, 311-314.
43. Rao, M.B.; Tanksale, A.M.; Ghatge, M.; Deshpande, V. Molecular and biotechnological aspects of microbial proteases. Microbiol. Mol. Biol. Rev., 1998, 62, 597-635.
44. Takahashi, K. In: Aspartic peptidases structure, function, biology and biomedical implications. Plenum Press: New York, 1995.
45. Fruton, J. A history of pepsin and related enzymes. Quart. Rev. Biol., 2002, 77, 127-147.
46. Sielecki, R.; Fujinanga, M.; Read, R.J.; James, M.N.G. Refined structure of porcine pepsinogenat 1.8 Å resolution. J. Mol. Biol., 1991, 219, 671-692.
47. Blundell, T., Cooper, J., Sali, A., and Zhu, Z. In: Structure and function of the aspartic proteases; Dunn, B.N. Ed.; Plenum Press: New York, 1991; Vol. 306, pp. 443.
48. Holm, I.; Ollo, R.; Panthier, J.; Rougeon, F. Evolution of aspartic proteases by gene duplication: the mouse renin gene is organized in two homologous clusters of four exons. EMBO J., 1984, 3, 557-562.
49. Veerapandian, B.; Cooper, J.; Sali, A.; Blundell, T.; Rosati, R.; Dominy, B.; Damon, D.; Hoover, D. Direct observation by X-ray analysis of the tetrahedral "intermediate" of aspartic proteinases. Protein Sci., 1992, 1, 322-328.
50. Northrop, D. Follow the protons: a low-barrier hydrogen bond unifies the mechanisms of the aspartic proteases. Accounts Chem. Res., 2001, 34, 790-797.
51. Dunn, B. Structure and mechanism of the pepsin-like family of aspartic peptidases. Chem. Rev., 2002, 102, 4431-4458.
52. Nguyen, J.T.; Hamada, Y.; Kimura, T.; Kiso, Y. Design of potent aspartic protease inhibitors to treat various diseases. Arch. Pharm. Chem. Life Sci., 2008, 341, 523-535.
53. MEROPS -The peptidase database: Realease 9.6. http://merops.sanger.ac.uk/ (Accessed June 26, 2012).
54. Fujinaga, M.; Chernaia, M.M.; Tarasova, N.I.; Mosimann, S.C.; James, M.N. Crystal structure of human pepsin and its complex with pepstatin. Protein Sci., 1995, 4, 960-972.
55. Jaskólski, M.; Tomasselli, A.G.; Sawyer, T.K.; Staples, D.G.; Heinrikson, R.L.; Schneider, J.; Kent, S.B.; Wlodawer, A. Structure at 2.5 A resolution of chemically synthesized human immunodeficiency virus type 1 protease complexed with a hydroxyethylenebased inhibitor. Biochemistry, 1991, 30, 1600-1609.
56. Steiner, H.; Kostka, M.; Romig, H. Basset, G.; Pesold, B.; Hardy, J.; Capell, A.; Meyn, L.; Grim M.L.; Baumeister, R.; Fechteler, K.; Haass, C. Glycine 384 is required for presenilin-1 function and is conserved in bacterial polytopic aspartic proteases. Nat. Cell. Biol., 2000, 2, 848-851.
57. Laudon, H.; Winblad, B.; Näslund, J. The Alzheimer's diseasesassociated b-secretase complex: functional domains in the presenilin 1 protein. Physiol. Behav., 2007, 92, 115-120.
58. Alves, C.R.; Corte-Real, S.; Bourguignon, S.C.; Chaves, C.S.; Saraiva, E.M. Leishmania amazonensis: early proteinase activities during promastigote-amastigote differentiation in vitro. Exp. Parasitol., 2005, 109, 38-48.
59. Savoia, D.; Allice, T; Tovo, P.A. Antileishmanial activity of HIV protease inhibitors. Int. J. Antimicrob. Agents, 2005, 26, 92-94.
60. Valdivieso, E.; Dagger, F.; Rascón, A. Leishmania mexicana: identification and characterization of an aspartic proteinase activity. Exp. Parasitol., 2007, 116, 77-82.
61. Trudel, N.; Garg, R.; Messier, N.; Sundar, S.; Ouellette, M.; Tremblay, M.J. Intracellular survival of Leishmania species that cause visceral leishmaniasis is significantly reduced by HIV-1 protease inhibitors. J. Infect. Dis., 2008, 198, 1292-1299.
62. Santos, L.O.; Marinho, F.A.; Altoé, E.F.; Vitório, B.S.; Alves, C.R.; Britto, C.; Motta, M.C.; Branquinha, M.H.; Santos, A.L.S.; d'Avila-Levy, C.M. HIV aspartic peptidase inhibitors interfere with cellular proliferation, ultrastructure and macrophage infection of Leishmania amazonensis. PLoS One, 2009, 4, e4918.
63. Valdivieso, E.; Rangel, A.; Moreno, J.; Saugar, J.M.; Cañavate, C.; Alvar, J.; Dagger, F. Effects of HIV aspartic-proteinase inhibitors on Leishmania sp. Exp. Parasitol., 2010, 126, 557-563.
64. Saboti-, J.; Kos, J. Microbial and fungal protease inhibitors: current and potential applications. Appl. Microbiol. Biotechnol., 2012, 93, 1351-1375.
65. Santos, A.L.S. Aspartic proteases of human pathogenic fungi are prospective targets for the generation of novel and effective antifungal inhibitors. Curr. Enz. Inhib., 2011, 7, 96-118.
66. Santos, A.L.S. HIV aspartic protease inhibitors as promising compounds against Candida albicans. World J. Biol. Chem., 2010, 1, 21-30.
67. Vermelho, A.B.; Branquinha, M.H.; d'Avila-Levy, C.M.; dos Santos, A.L.S.; Paraguai de Souza Dias, E.; Nogueira de Melo, A.C. Biological roles of peptidases in trypanosomatids. Open Parasitol. J., 2010, 4, 5-23.
68. Santos, A.L.S.; d'Avila-Levy, C.M.; Branquinha, M.H. In: Calpain-like proteins in trypanosomatids: effects of calpain inhibitors on the parasites' physiology and motivations for their possible application as chemotherapeutic agents. Cohen, J.B.; Ryseck, L.P., Eds.; Nova Science Publishers: New York, 2011; pp. 77-104.
69. Santos, A.L.S.; d'Avila-Levy, C.M.; Branquinha, M.H. In: Antitrypanosomatid properties of cystatin superfamily: implications on parasite development and virulence. Cohen, J.B.; Ryseck, L.P., Eds.; Nova Science Publishers: New York, 2011; pp. 41-76.
70. Santos, A.L.S. In: Aspartic peptidase inhibitors as potential bioactive pharmacological compounds against human fungal pathogens. Ahmad, I.; Owais, M.; Shahid, M.; Aqil, F. Eds.; Springer-Verlag: Berlin, 2010; pp. 289-326.
71. Vermelho, A.B.; Giovanni De Simone, S.; d'Avila-Levy, C.M.; Santos, A.L.S.; Nogueira de Melo, A.C.; Silva-Junior, F.P.; Bom, E.P.; Branquinha, M.H. Trypanosomatidae peptidases: a target for drugs development. Curr. Enz. Inhib., 2007, 3, 19-48.
72. Abbenante, G.; Fairlie, D.P. Protease inhibitors in the clinic. Med. Chem., 2005, 1, 71-104.
73. Flexner, C. HIV-protease inhibitors. N. Engl. J. Med., 1998, 338, 1281-1292.
74. McKerrow, J.H.; Engel, J.C.; Caffrey, C.R. Cysteine protease inhibitors as chemotherapy for parasitic infections. Bioorg. Med. Chem., 1999, 7, 639-644.
75. Coombs, G.H.; Goldberg, D.E.; Klemba, M.; Berry, C.; Kay, J.; Mottram, J.C. Aspartic proteases of Plasmodium falciparum and other parasitic protozoa as drug targets. Trends Parasitol., 2001, 17, 532-537.
76. Stewart, K.; Abad-Zapatero, C. Candida proteases and their inhibition: prospects for antifungal therapy. Curr. Med. Chem., 2001, 8, 941-948.
77. Dash, C.; Kulkarni, A.; Dunn, B.; Rao, M. Aspartic peptidase inhibitors: implications in drug development. Crit. Rev. Biochem. Mol. Biol., 2003, 38, 89-119.
78. Pozio, E.; Morales, M.A. The impact of HIV-protease inhibitors on opportunistic parasites. Trends Parasitol., 2005, 21, 58-63.
79. Mastrolorenzo, A.; Rusconi, S.; Scozzafava, A.; Barbaro, G.; Supuran, C.T. Inhibitors of HIV-1 protease: current state of the art 10 years after their introduction. From antiretroviral drugs to antifungal, antibacterial and antitumor agents based on aspartic protease inhibitors. Curr. Med. Chem., 2007, 14, 2734-2748.
80. Nguyen, J.T.; Hamada, Y.; Kimura, T.; Kiso, Y. Design of potent aspartic protease inhibitors to treat various diseases. Arch. Pharm. (Weinheim), 2008, 341, 523-535.
81. McKerrow, J.H.; Rosenthal, P.J.; Swenerton, R.; Doyle, P. Development of protease inhibitors for protozoan infections. Curr. Opin. Infect. Dis., 2008, 21, 668-672.
82. Powderly, W.G; Landay, A.; Lederman, M.M. Recovery of the immune system with antiretroviral therapy. The end of opportunism? JAMA, 1998, 280, 72-77.
83. Mastroianni, C.M.; Lichtner, M.; Mengoni, F.; D'Agostino, C., Forcina, G.; d'Ettorre, G.; Santopadre, P.; Vullo, V. Improvement in neutrophil and monocyte function during highly active antiretroviral treatment of HIV-1 infected patients. AIDS, 1999, 13, 883- 890.
84. Mezzaroma, I.; Carlesimo, M.; Pinter, E.; Alario, C.; Sacco, G.; Muratori, D.S.; Bernardi, M.L.; Paganelli, R.; Aiuti, F. Long-term evaluation of T-cell subsets and T-cell function after HAART in advanced stage HIV-1 disease. AIDS, 1999, 13, 1187-1193.
85. Malhotra, U.; Berrei, M.M.; Huang, Y.; Maree, J.; Brown, D.J.; Ap, S.; Musey, L.; Schacker, T.; Corey, L.; McElrath, M.J. Effect of combination antiretroviral therapy on T-cell immunity in acute human immunodeficiency virus type 1 infection. J. Infect. Dis., 2000, 181, 121-131.
86. Alvar, J.; Aparício, P.; Aseffa, A.; Den Bôer, M.; Cañavate, C.; Dedet, J.P.; Gradoni, L.; Ter Horst, R.; López-Vélez, R.; Moreno, J. The relationship between leishmaniasis and AIDS: the second 10 years. J. Clin. Microbiol. Rev., 2008, 21, 334-359.
87. Nissapatorn, V; Sawangjaroen, N. Parasitic infections in HIV infected individuals: Diagnostic & therapeutic challenges. Indian J. Med. Res., 2011, 134, 878-897.
88. Palella, F.J.Jr.; Delaney, K.M.; Moorman, A.C.; Loveless, M.O.; Fuhrer, J.; Satten, G.A.; Aschman, D.J.; Holmberg S.D. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigation. N. Engl. J. Med., 1998, 338, 853-886.
89. Casolari, C.; Rossi, T.; Baggio, G.; Coppi, A.; Zandomeneghi, G.; Ruberto, A.I.; Farina, C.; Fabio, G.; Zanca, A.; Castelli, M. Interaction between saquinavir and antimycotic drugs on C. albicans and C. neoformans strains. Pharmacol. Res., 2004, 50, 605-610.
90. Falkensammer, B.; Pilz, G.; Bekti-, J.; Imwidthaya, P.; Jöhrer, K.; Speth, C; Lass-Flörl, C.; Dierich, M.P.; Würzner, R. Absent reduction by HIV protease inhibitors of Candida albicans adhesion to endothelial cells. Mycoses, 2007, 50, 172-177.
91. Cenci, E.; Francisci, D.; Belfiori, B.; Pierucci, S.; Baldelli, F.; Bistoni, F.; Vecchiarelli, A. Tipranavir exhibits different effects on opportunistic pathogenic fungi. J. Infect., 2008, 56, 58-64.
92. Tsang, C.S.; Hong, I. HIV protease inhibitors differentially inhibit adhesion of Candida albicans to acrylic surfaces. Mycoses., 2010, 53, 488-494.
93. Braga-Silva, L.A.; Mogami, S.S.; Valle, R.S.; Silva-Neto, I.D.; Santos, A.L.S. Multiple effects of amprenavir against Candida albicans. FEMS Yeast Res., 2010, 10, 221-224.
94. Moreno, M.; Gonzalez, V.M. Advances on Aptamers Targeting Plasmodium and Trypanosomatids. Curr. Med. Chem., 2011, 18, 5003-5010.
95. Peyrottes, S.; Caldarelli, S.; Wein, S.; Périgaud, C.; Pellet, A.; Vial, H. Choline Analogues in Malaria Chemotherapy. Curr. Pharm. Desgn., 2012, 18, 3454-3466.
96. Teixeira, C.; Gomes, J.R.B.; Gomes, P. Falcipains, Plasmodium falciparum Cysteine proteases as key drug targets against malaria. Curr. Med. Chem., 2011, 18, 1555-1572.
97. Alam, A.; Goyal, M.; Iqbal, M.S.; Pal, C.; Dey, S.; Bindu, S.; Maity, P.; Bandyopadhyay, U. Novel antimalarial drug targets: hope for new antimalarial drugs. Expert. Rev. Clin. Pharmacol., 2009, 2, 469-489.
98. Bekti-, J.; Lell, C.P.; Fuchs, A.; Stoiber, H.; Speth, C.; Lass-Flörl, C.; Borg-von Zepelin, M.; Dierich, M.P.; Würzner, R. HIV protease inhibitors attenuate adherence of Candida albicans to epithelial cells in vitro. FEMS Immunol. Med. Microbiol., 2001, 31, 65-71.
99. Borg-von Zepelin, M.; Meyer, I.; Thomssen, R.; Würzner, R.; Sanglard, D.; Telenti, A.; Monod, M. HIV-Protease inhibitors reduce cell adherence of Candida albicans strains by inhibition of yeast secreted aspartic proteases. J. Invest. Dermatol., 1999, 113, 747-751.
100. Monod M, Borg-von Zepelin M, Telenti A, Sanglard D. The inhibition of Candida-albicans-secreted aspartic proteases by three different HIV protease inhibitors. Dermatology, 1999, 198, 412-414.
101. Braga-Silva, L.A.; Santos, A.L.S. Aspartic protease inhibitors as potential anti-Candida albicans drugs: impacts on fungal biology, virulence and pathogenesis. Curr. Med. Chem., 2011, 18, 2401-2419.
102. Girardi, E.; Antonucci, G.; Vanacore, P.; Libanore, M.; Errante, I.; Matteelli, A.; Ippolito, G. Impact of combination antiretroviral therapy on the risk of tuberculosis among persons with HIV infection. Gruppo Italiano di Studio Tubercolosi e AIDS (GISTA). AIDS, 2000, 14, 1985-1991.
103. Kirk, O.; Gatell, J.M.; Mocroft, A.; Pedersen, C.; Proenca, R.; Brettle, R.P.; Barton, S.E.; Sudre, P.; Phillips, A.N. Infections with Mycobacterium tuberculosis and Mycobacterium avium among HIV-infected patients after the introduction of highly active antiretroviral therapy. EuroSIDA Study Group JD. Am. J. Respir. Crit. Care Med., 2000, 162, 865-872.
104. Erratum in: Am. J. Respir. Crit. Care Med., 2003, 167, 1719.
105. Shen, Y.; Shen, L.; Sehgal, P.; Zhou, D.; Simon, M.; Miller, M.; Enimi, E.A.; Henckler, B.; Chalifoux, L.; Sehgal, N.; Gastron, M.; Letvin, N.L.; Chen, Z.W. Antiretroviral agents restore Mycobacterium-specific T cell immune responses and facilitate controlling a fatal tuberculosis-like disease in Macaques coinfected with simianimmunodeficiency virus and Mycobacterium bovis BCG. J. Virol., 2001, 75, 8690-8696.
106. Kabbesh, M.; Koomer, A.; Molteni, A.; Amajoyi, R.; Quinn, T.; Herndon, B. The effect of treatment with a protease inhibitor on mycobacterial infection. Diagn. Microbiol. Infect. Dis., 2005, 51, 251-258.
107. Santos, L.O.; Vitório, B.S.; Branquinha, M.H.; Pedrozo, C.; Santos, A.L.S.; d'Avila-Levy, C.M. Nelfinavir, an HIV aspartyl peptidase inhibitor, is effective in inhibiting the multiplication and aspartyl peptidase activity of several Leishmania species, including strains obtained from HIV-positive patients. J. Antmicrob. Chemother., 2013, 68, 348-353.
108. White, R.E.; Powell, D.J.; Berry, C. HIV proteinase inhibitors target the Ddi1-like protein of Leishmania parasites. FASEB J., 2011, 25, 1729-1736.
109. Perteguer, M.J.; Gómez-Puertas, P.; Cañavate, C.; Dagger, F.; Gárate, T.; Valdivieso, E. Ddi1-like protein from Leishmania major is an active aspartyl proteinase. Cell Stress Chaperones., 2012, [Epub ahead of print].
110. Falutz J. Management of fat accumulation in patients with HIV infection. Curr. HIV/AIDS Rep., 2011, 8, 200-208.
111. Kumar, P.; Lodge, R.; Trudel, N.; Ouellet, M.; Ouellette, M.; Tremblay, M.J. Nelfinavir, an HIV-1 protease inhibitor, induces oxidative stress-mediated, caspase-independent apoptosis in Leishmania amastigotes. PLoS. Negl. Trop. Dis., 2010, 4, e642.
112. Demarchi, I.G.; Silveira, T.G.; Ferreira, I.C.; Lonardoni, M.V. Effect of HIV protease inhibitors on New World Leishmania. Parasitol Int., 2012, 61, 538-544.
113. Alvarez, V.E.; Niemirowicz, G.T.; Cazzulo, J.J. The peptidases of Trypanosoma cruzi: digestive enzymes, virulence factors, and mediators of autophagy and programmed cell death. Biochim. Biophys. Acta., 2012, 1824, 195-206.
114. Pinho, R.T.; Beltramini, L.M.; Alves, C.R.; De-Simone, S.G. Trypanosoma cruzi: isolation and characterization of aspartic proteases. Exp. Parasitol., 2009, 122, 128-133.
115. El-Sayed, N.M.; Myler, P.J.; Bartholomeu, D.C.; Nilsson, D.; Aggarwal, G.; Tran, A.N.; Ghedin, E.; Worthey, E.A.; Delcher, A.L.; Blandin, G.; Westenberger, S.J.; Caler, E.; Cerqueira, G.C.; Branche, C.; Haas, B.; Anupama, A.; Arner, E.; Aslund, L.; Attipoe, P.; Bontempi, E.; Bringaud, F.; Burton, P.; Cadag, E.; Campbell, D.A.; Carrington, M.; Crabtree, J.; Darban, H.; da Silveira, J.F.; de Jong, P.; Edwards, K.; Englund, P.T.; Fazelina, G.; Feldblyum, T.; Ferella, M.; Frasch, A.C.; Gull, K.; Horn, D.; Hou, L.; Huang, Y.; Kindlund, E.; Klingbeil, M.; Kluge, S.; Koo, H.; Lacerda, D.; Levin, M.J.; Lorenzi, H.; Louie, T.; Machado, C.R.; McCulloch, R.; McKenna, A.; Mizuno, Y.; Mottram, J.C.; Nelson, S.; Ochaya, S.; Osoegawa, K.; Pai, G.; Parsons, M.; Pentony, M.; Pettersson, U.; Pop, M.; Ramirez, J.L.; Rinta, J.; Robertson, L.; Salzberg, S.L.; Sanchez, D.O.; Seyler, A.; Sharma, R.; Shetty, J.; Simpson, A.J.; Sisk, E.; Tammi, M.T.; Tarleton, R.; Teixeira, S.; Van Aken, S.; Vogt, C.; Ward, P.N.; Wickstead, B.; Wortman, J.; White, O.; Fraser, C.M.; Stuart, K.D.; Andersson, B. The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas' disease. Science, 2005, 309, 409-415.
116. Sangenito, L.S.; Gonçalves, K.C.; Abi-Chacra, E.A.; Sodré, C.L.; d'Avila-Levy, C.M.; Branquinha, M.H.; Santos, A.L.S. Multiple effects of pepstatin A on Trypanosoma cruzi epimastigote forms. Parasitol. Res., 2012, 110, 2533-2540.
117. Andrade, Z,A. Immunopathology of Chagas' disease. Mem. Inst. Oswaldo Cruz., 1999, 1, 71-80.
118. Fampa, P.; Santos, A.L.S.; Ramirez, M.I. Trypanosoma cruzi: ubiquity expression of surface cruzipain molecules in TCI and TCII field isolates. Parasitol. Res., 2010, 107, 443-447.
119. Kikuchi, S.A.; Sodré, C.L.; Kalume, D.E.; Elias, C.G.; Santos, A.L.S.; de Nazaré Soeiro, M.; Meuser, M.; Chapeaurouge, A.; Perales, J.; Fernandes, O. Proteomic analysis of two Trypanosoma cruzi zymodeme 3 strains. Exp. Parasitol., 2010, 126, 540-551.
120. Tumbarello, M.; Tacconelli, E.; Bertagnolio, S.; Cauda, R. Highly active antiretroviral therapy decreases the incidence of visceral leishmaniasis in HIV-infected individuals. AIDS, 2000, 14, 2948-2950.
121. Rosenthal, E.; Tempesta, S.; del Giudice, P.; Marty, P.; Desjeux, P.; Pradier, C.; Le Fichoux, Y.; Jill-Patrice, C. Declining incidence of visceral leishmaniasis in HIV-infected individuals in the era of highly active antiretroviral therapy. AIDS., 2001, 15, 1184-1185.
122. ter Horst, R.; Collin, S.M.; Ritmeijer, K.; Bogale, A.; Davidson, R.N. Concordant HIV infection and visceral leishmaniasis in Ethiopia: the influence of antiretroviral treatment and other factors on outcome. Clin. Infect. Dis., 2008, 46, 1702-1709.
123. Larkin, M.A.; Blackshields, G.; Brown, N.P.; Chenna, R.; McGettigan, P.A.; McWilliam, H.; Valentin, F.; Wallace, I.M.; Wilm, A.; Lopez, R.; Thompson, J.D.; Gibson, T.J.; Higgins, D.G. Clustal W and Clustal X version 2.0. Bioinformatics, 2007, 23, 2947-2948.
124. Tamura, K.; Peterson, D.; Peterson, N.; Stecher, G.; Nei, M.; Kumar, S. MEGA5: Molecular Evolutionary Genetics Analysis using Maximum Likelihood, Evolutionary Distance, and Maximum Parsimony Methods. Mol. Biol. Evol., 2011, 28, 2731-2739.
125. Saitou, N.; Nei, M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol. Biol. Evol., 1987, 4, 406-425.