Generic placeholder image

Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Repositioning of HIV Aspartyl Peptidase Inhibitors for Combating the Neglected Human Pathogen Trypanosoma cruzi

Author(s): Leandro S. Sangenito*, Rubem F.S. Menna-Barreto, Cláudia M. d'Avila-Levy, Marta H. Branquinha* and André L.S. Santos*

Volume 26, Issue 36, 2019

Page: [6590 - 6613] Pages: 24

DOI: 10.2174/0929867326666190610152934

Price: $65


Chagas disease, caused by the flagellate parasite Trypanosoma cruzi, is a wellknown neglected tropical disease. This parasitic illness affects 6-7 million people and can lead to severe myocarditis and/or complications of the digestive tract. The changes in its epidemiology facilitate co-infection with the Human Immunodeficiency Virus (HIV), making even more difficult the diagnosis and prognosis. The parasitic infection is reactivated in T. cruzi/HIV co-infection, with the appearance of unusual manifestations in the chronic phase and the exacerbation of classical clinical signs. The therapeutic arsenal to treat Chagas disease, in all its clinical forms, is restricted basically to two drugs, benznidazole and nifurtimox. Both drugs are extremely toxic and the therapeutic efficacy is still unclear, making the clinical treatment a huge issue to be solved. Therefore, it seems obvious the necessity of new tangible approaches to combat this illness. In this sense, the repositioning of approved drugs appears as an interesting and viable strategy. The discovery of Human Immunodeficiency Virus Aspartyl Peptidase Inhibitors (HIV-PIs) represented a milestone in the treatment of Acquired Immune Deficiency Syndrome (AIDS) and, concomitantly, a marked reduction in both the incidence and prevalence of important bacterial, fungal and parasitic co-infections was clearly observed. Taking all these findings into consideration, the present review summarizes the promising and beneficial data concerning the effects of HIV-PIs on all the evolutionary forms of T. cruzi and in important steps of the parasite’s life cycle, which highlight their possible application as alternative drugs to treat Chagas disease.

Keywords: Chagas disease, Trypanosoma cruzi, HIV-PIs, drug repositioning, mode of action, physiological alterations.

Rassi, A., Jr; Rassi, A.; Marcondes de Rezende, J. American trypanosomiasis (Chagas disease). Infect. Dis. Clin. North Am., 2012, 26(2), 275-291.
[] [PMID: 22632639]
Gorla, D.; Noireau, F. Geographic distribution of triatominae vectors in America. 2010, 197-221.
Dias, J.C.; Amato Neto, V.; Luna, E.J. [Alternative transmission mechanisms of Trypanosoma cruzi in Brazil and proposals for their prevention Rev. Soc. Bras. Med. Trop., 2011, 44(3), 375-379.
[] [PMID: 21625803]
Organizacion Panamericana de la Salud, Estimacion cuantitativa de la enfermedad de chagas en las Americas. fact, 2017.
World health organization Tropical Disease Research. Program for research and training tropical disease (TDR). Fact sheet FS340, 2017.
Haberland, A.; Saravia, S.G.; Wallukat, G.; Ziebig, R.; Schimke, I. Chronic chagas disease: from basics to laboratory medicine. Clin. Chem. Lab. Med., 2013, 51(2), 271-294.
[] [PMID: 23045386]
Andrade, D.V.; Gollob, K.J.; Dutra, W.O. Acute chagas disease: new global challenges for an old neglected disease. PLoS Negl. Trop. Dis., 2014, 8(7)e3010
[] [PMID: 25077613]
Lattes, R.; Lasala, M.B. Chagas disease in the immunosuppressed patient. Clin. Microbiol. Infect., 2014, 20(4), 300-309.
[] [PMID: 24602129]
Ramos, A.N. Jr [Inclusion of Chagas’ disease reactivation as a condition for AIDS case definition to epidemiological surveillance in Brazil Rev. Soc. Bras. Med. Trop., 2004, 37(2), 192-193.
[] [PMID: 15094911]
Harms, G.; Feldmeier, H. The impact of HIV infection on tropical diseases. Infect. Dis. Clin. North Am., 2005, 19(1), 121-135 ix.
[] [PMID: 15701550]
Sartori, A.M.; Ibrahim, K.Y.; Nunes Westphalen, E.V.; Braz, L.M.; Oliveira, O.C.J.R. Jr.; Gakiya, E.; Lopes, M.H.; Shikanai-Yasuda, M.A. Manifestations of Chagas disease (American trypanosomiasis) in patients with HIV/AIDS. Ann. Trop. Med. Parasitol., 2007, 101(1), 31-50.
[] [PMID: 17244408]
Pérez-Molina, J.A. Management of Trypanosoma cruzi coinfection in HIV-positive individuals outside endemic areas. Curr. Opin. Infect. Dis., 2014, 27(1), 9-15.
[] [PMID: 24275694]
Silva, N.; O’Bryan, L.; Medeiros, E.; Holand, H.; Suleiman, J.; de Mendonca, J.S.; Patronas, N.; Reed, S.G.; Klein, H.G.; Masur, H.; Badaro, R. Trypanosoma cruzi meningoencephalitis in HIV-infected patients. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol., 1999, 20(4), 342-349.
[] [PMID: 10096578]
Cordova, E.; Boschi, A.; Ambrosioni, J.; Cudos, C.; Corti, M. Reactivation of Chagas disease with central nervous system involvement in HIV-infected patients in Argentina, 1992-2007. Int. J. Infect. Dis., 2008, 12(6), 587-592.
[] [PMID: 18337139]
Cançado, J.R.; Brenner, Z.; Andrade, A.Z.; Barral-Netto, M. Trypanosoma cruzi e Doença de Chagas, 2nd ed; Guanabara Koogan: AS, 2000.
Salomon, C.J. First century of Chagas’ disease: an overview on novel approaches to nifurtimox and benzonidazole delivery systems. J. Pharm. Sci., 2012, 101(3), 888-894.
[] [PMID: 22161779]
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.
[] [PMID: 22760123]
Sobrinho, J.L.S.; Fontes, D.A.F.; de Lyra, M.A.M.; La Roca-Soares, M.F.; Neto, P.J.R. Chagas disease: 100 years from its discovery. Rev. Bras. Farm., 2009, 4, 283-289.
ALP. M.; Göker, H., Brun, R., & Yıldız, S. Synthesis and antiparasitic and antifungal evaluation of 20-arylsubstituted-1H,10H-[2,50]bisbenzimidazolyl-5-carboxamidines. Eur. J. Med. Chem., 2009, 44, 2002-2008.
[] [PMID: 19010569]
Torreele, E.; Bourdin Trunz, B.; Tweats, D.; Kaiser, M.; Brun, R.; Mazué, G.; Bray, M.A.; Pécoul, 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
[] [PMID: 21200426]
Bahia, M.T.; de Andrade, I.M.; Martins, T.A.; do Nascimento, Á.F. Diniz, Lde.F.; Caldas, I.S.; Talvani, A.; Trunz, B.B.; Torreele, E.; Ribeiro, I. Fexinidazole: a potential new drug candidate for Chagas disease. PLoS Negl. Trop. Dis., 2012, 6(11)e1870
[] [PMID: 23133682]
Schmidt, T.J.; Khalid, S.A.; Romanha, A.J.; Alves, T.M.; Biavatti, M.W.; Brun, R.; Da Costa, F.B.; de Castro, S.L.; Ferreira, V.F.; de Lacerda, M.V.; Lago, J.H.; Leon, L.L.; Lopes, N.P. das Neves Amorim, R.C.; Niehues, M.; Ogungbe, I.V.; Pohlit, A.M.; Scotti, M.T.; Setzer, W.N.; de N C Soeiro, M.; Steindel, M.; Tempone, A.G. The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases - part II. Curr. Med. Chem., 2012, 19(14), 2176-2228.
[] [PMID: 22414104]
Ogungbe, I.V.; Setzer, W.N. The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases-part iii: in-silico molecular docking investigations. Molecules, 2016, 19, 21(10), pii E1389.
[] [PMID: 27775577]
Nabavi, S.F.; Sureda, A.; Daglia, M.; Izadi, M.; Rastrelli, L.; Nabavi, S.M. Flavonoids and chagas’ disease: the story so far! Curr. Top. Med. Chem., 2017, 17(4), 460-466.
[] [PMID: 27558676]
Ekins, S.; Williams, A.J.; Krasowski, M.D.; Freundlich, J.S. In silico repositioning of approved drugs for rare and neglected diseases. Drug Discov. Today, 2011, 16(7-8), 298-310.
[] [PMID: 21376136]
Arrowsmith, J.; Harrison, R. Drug repositioning: the business case and current strategies to repurpose shelved candidates and marketed drugs In: Drug Repositioning: Bringing New Life to Shelved Assets and Existing Drugs, Michael J. Barratt, Donald E. Frail, Eds. John Wiley Sons, Inc. 2012, pp. 7-32.
Gouveia, M.J.; Brindley, P.J.; Gärtner, F.; Costa, J.M.C.D.; Vale, N. Drug repurposing for schistosomiasis: combinations of drugs or biomolecules. Pharmaceutical, 2018, 11(1)E15
[] [PMID: 29401734]
Nosengo, N. Can you teach old drugs new tricks? Nature, 2016, 534(7607), 314-316.
[] [PMID: 27306171]
Yella, J.K.; Yaddanapudi, S.; Wang, Y.; Jegga, A.G. Changing trends in computational drug repositioning. Pharmaceuticals (Basel), 2018, 11(2)pii E57
[] [PMID: 29874824]
Bellera, C.L.; Sbaraglini, M.L.; Balcazar, D.E.; Fraccaroli, L.; Vanrell, M.C.; Casassa, A.F.; Labriola, C.A.; Romano, P.S.; Carrillo, C.; Talevi, A. High-throughput drug repositioning for the discovery of new treatments for Chagas disease. Mini Rev. Med. Chem., 2015, 15(3), 182-193.
[] [PMID: 25769967]
Sbaraglini, M.L.; Vanrell, M.C.; Bellera, C.L.; Benaim, G.; Carrillo, C.; Talevi, A.; Romano, P.S. Neglected tropical protozoan diseases: drug repositioning as a rational option. Curr. Top. Med. Chem., 2016, 16(19), 2201-2222.
[] [PMID: 26881713]
Dichiara, M.; Marrazzo, A.; Prezzavento, O.; Collina, S.; Rescifina, A.; Amata, E. Repurposing of human kinase inhibitors in neglected protozoan diseases. ChemMedChem, 2017, 12(16), 1235-1253.
[] [PMID: 28590590]
Ferreira, L.G.; Andricopulo, A.D. Drug repositioning approaches to parasitic diseases: a medicinal chemistry perspective. Drug Discov. Today, 2016, 21(10), 1699-1710.
[] [PMID: 27365271]
Tomimori-Yamashita, J.; Deps, P.D.; Almeida, D.R.; Enokihara, M.M.; De Seixas, M.T.; Freymüller, E. Cutaneous manifestation of Chagas’ disease after heart transplantation: successful treatment with allopurinol. Br. J. Dermatol., 1997, 137(4), 626-630.
[] [PMID: 9390344]
Urbina, J.A. Ergosterol biosynthesis and drug development for Chagas disease. Mem. Inst. Oswaldo Cruz, 2009, 104(Suppl. 1), 311-318.
[] [PMID: 19753490]
Dakshanamurthy, S.; Issa, N.T.; Assefnia, S.; Seshasayee, A.; Peters, O.J.; Madhavan, S.; Uren, A.; Brown, M.L.; Byers, S.W. Predicting new indications for approved drugs using a proteochemometric method. J. Med. Chem., 2012, 55(15), 6832-6848.
[] [PMID: 22780961]
Végner, L.; Peragovics, Á.; Tombor, L.; Jelinek, B.; Czobor, P.; Bender, A.; Simon, Z.; Málnási-Csizmadia, A. Experimental confirmation of new drug-target interactions predicted by drug profile matching. J. Med. Chem., 2013, 56(21), 8377-8388.
[] [PMID: 24088053]
Flexner, C. HIV-protease inhibitors. N. Engl. J. Med., 1998, 338(18), 1281-1292.
[] [PMID: 9562584]
Zhan, P.; Pannecouque, C.; De Clercq, E.; Liu, X. Anti-HIV drug discovery and development: current innovations and future trends. J. Med. Chem., 2016, 59(7), 2849-2878.
[] [PMID: 26509831]
Tsantrizos, Y.S. Peptidomimetic therapeutic agents targeting the protease enzyme of the human immunodeficiency virus and hepatitis C virus. Acc. Chem. Res., 2008, 41(10), 1252-1263.
[] [PMID: 18681464]
Ebrahim, O.; Mazanderani, A.H. Recent developments in HIV treatment and their dissemination in poor countries. Infect. Dis. Rep., 2013, 5(Suppl. 1)e2
[] [PMID: 24470966]
Palella, F.J.J.R., Jr; Delaney, K.M.; Moorman, A.C.; Loveless, M.O.; Fuhrer, J.; Satten, G.A.; Aschman, D.J.; Holmberg, S.D. HIV outpatient study investigators. declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N. Engl. J. Med., 1998, 338(13), 853-860.
[] [PMID: 9516219]
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(26), 2734-2748.
[] [PMID: 18045120]
Alfonso, Y.; Monzote, L. HIV protease inhibitors: effect on the opportunistic protozoan parasites. Open Med. Chem. J., 2011, 5, 40-50.
[] [PMID: 21629510]
Santos, A.L.S.; d’Avila-Levy, C.M.; Kneipp, L.F.; Sodré, C.L.; Sangenito, L.S.; Branquinha, M.H. The widespread anti-protozoal action of HIV aspartic peptidase inhibitors: focus on Plasmodium spp., Leishmania spp. and Trypanosoma cruzi. Curr. Top. Med. Chem., 2017, 17(11), 1303-1317.
[] [PMID: 27784256]
Alvar, J.; Cañavate, C.; Gutiérrez-Solar, B.; Jiménez, M.; Laguna, F.; López-Vélez, R.; Molina, R.; Moreno, J. Leishmania and human immunodeficiency virus coinfection: the first 10 years. Clin. Microbiol. Rev., 1997, 10(2), 298-319.
[] [PMID: 9105756]
Pintado, V.; López-Vélez, R. [Visceral leishmaniasis associated with human immunodeficiency virus infection Enferm. Infecc. Microbiol. Clin., 2001, 19(7), 353-357.
[] [PMID: 11747803]
Pintado, V.; Martín-Rabadán, P.; Rivera, M.L.; Moreno, S.; Bouza, E. Visceral leishmaniasis in human immunodeficiency virus (HIV)-infected and non-HIV-infected patients. A comparative study. Medicine (Baltimore), 2001, 80(1), 54-73.
[] [PMID: 11204503]
Cruz, I.; Nieto, J.; Moreno, J.; Cañavate, C.; Desjeux, P.; Alvar, J. Leishmania/HIV co-infections in the second decade. Indian J. Med. Res., 2006, 123(3), 357-388.
[PMID: 16778317]
Monari, C.; Pericolini, E.; Bistoni, G.; Cenci, E.; Bistoni, F.; Vecchiarelli, A. Influence of indinavir on virulence and growth of Cryptococcus neoformans. J. Infect. Dis., 2005, 191(2), 307-311.
[] [PMID: 15609242]
Hommer, V.; Eichholz, J.; Petry, F. Effect of antiretroviral protease inhibitors alone, and in combination with paromomycin, on the excystation, invasion and in vitro development of Cryptosporidium parvum. J. Antimicrob. Chemother., 2003, 52(3), 359-364.
[] [PMID: 12888587]
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(6), 605-610.
[] [PMID: 15501699]
Gascon, J.; Bern, C.; Pinazo, M.J. Chagas disease in Spain, the United States and other non-endemic countries. Acta Trop., 2010, 115(1-2), 22-27.
[] [PMID: 19646412]
Schmunis, G.A.; Yadon, Z.E. Chagas disease: A Latin American health problem becoming a world health problem. Acta Trop., 2010, 115(1-2), 14-21.
[] [PMID: 19932071]
Bern, C. Chagas disease in the immunosuppressed host. Curr. Opin. Infect. Dis., 2012, 25(4), 450-457.
[] [PMID: 22614520]
Spina-França, A.; Livramento, J.A.; Machado, L.R.; Yassuda, N. Anticorpos α-Trypanosoma cruzi no líquido cefalorraqueano. Arq. Neuro-Psiquiat., 1988, 46(4), 374-378.
Livramento, J.A.; Machado, L.R.; Spina-França, A. Anormalidades do líquido cefalorraqueano em 170 casos de AIDS. Arq. Neuropsiquiatr., 1989, 47(3), 326-331.
[] [PMID: 2619610]
Almeida, E.A.; Ramos Júnior, A.N.; Correia, D.; Shikanai-Yasuda, M.A. Co-infection Trypanosoma cruzi/HIV: systematic review (1980-2010). Rev. Soc. Bras. Med. Trop., 2011, 44(6), 762-770.
[] [PMID: 22231251]
Corti, M.; Yampolsky, C. Prolonged survival and immune reconstitution after chagasic meningoencephalitis in a patient with acquired immunodeficiency syndrome. Rev. Soc. Bras. Med. Trop., 2006, 39(1), 85-88.
[] [PMID: 16501775]
Olga López, M. Meningoencefalitis chagásica en un paciente con infeccion por VIH/SIDA con sobrevida a tres años: Caso clínico. “Three-year survival of a patient with HIV and chagasic meningoencephalitis: Case report. Rev. Chilena Infectol., 2010, 27(2), 160-164.
Yasukawa, K.; Patel, S.M.; Flash, C.A.; Stager, C.E.; Goodman, J.C.; Woc-Colburn, L. Trypanosoma cruzi meningoencephalitis in a patient with acquired immunodeficiency syndrome. Am. J. Trop. Med. Hyg., 2014, 91(1), 84-85.
[] [PMID: 24891470]
Buccheri, R.; Kassab, M.J.; Freitas, V.L.; Silva, S.C.; Bezerra, R.C.; Khoury, Z.; Shikanai-Yasuda, M.A.; Vidal, J.E. Chagasic meningoencephalitis inan hiv infected patient with moderateimmunosuppression: Prolonged survival and challenges in the HAART era. Rev. Inst. Med. Trop. São Paulo, 2015, 57(6), 531-535.
[] [PMID: 27049711]
Harms, G.; Feldmeier, H. HIV infection and tropical parasitic diseases - deleterious interactions in both directions? Trop. Med. Int. Health, 2002, 7(6), 479-488.
[] [PMID: 12031069]
Andreani, G.; Lodge, R.; Richard, D.; Tremblay, M.J. Mechanisms of interaction between protozoan parasites and HIV. Curr. Opin. HIV AIDS, 2012, 7(3), 276-282.
[] [PMID: 22418447]
Sangenito, L.S.; Menna-Barreto, R.F.; D, Avila-Levy. C.M.; Santos, A.L.; Branquinha, M.H. Decoding the anti-Trypanosoma cruzi action of HIV peptidase inhibitors using epimastigotes as a model. PLoS One, 2014, 9(12)e113957
[] [PMID: 25464510]
Zingales, B.; Andrade, S.G.; Briones, M.R.S.; Campbell, D.A.; Chiari, E.; Fernandes, O.; Guhl, F.; Lages-Silva, E.; Macedo, A.M.; Machado, C.R.; Miles, M.A.; Romanha, A.J.; Sturm, N.R.; Tibayrenc, M.; Schijman, A.G. Second satellite meeting. A new consensus for Trypanosoma cruzi intraspecific nomenclature: second revision meeting recommends TcI to TcVI. Mem. Inst. Oswaldo Cruz, 2009, 104(7), 1051-1054.
[] [PMID: 20027478]
Sangenito, L.S.; Gonçalves, K.C.; Abi-Chacra, E.A.; Sodré, C.L.; d’Avila-Levy, C.M.; Branquinha, M.H.; Santos, A.L. Multiple effects of pepstatin A on Trypanosoma cruzi epimastigote forms. Parasitol. Res., 2012, 110(6), 2533-2540.
[] [PMID: 22205353]
Bellera, C.L.; Balcazar, D.E.; Vanrell, M.C.; Casassa, A.F.; Palestro, P.H.; Gavernet, L.; Labriola, C.A.; Gálvez, J.; Bruno-Blanch, L.E.; Romano, P.S.; Carrillo, C.; Talevi, A. Computer-guided drug repurposing: identification of trypanocidal activity of clofazimine, benidipine and saquinavir. Eur. J. Med. Chem., 2015, 93, 338-348.
[] [PMID: 25707014]
Clevenbergh, P.; Mouly, S.; Sellier, P.; Badsi, E.; Cervoni, J.; Vincent, V.; Trout, H.; Bergmann, J.F. Improving HIV infection management using antiretroviral plasma drug levels monitoring: a clinician’s point of view. Curr. HIV Res., 2004, 2(4), 309-321.
[] [PMID: 15544452]
Wensing, A.M.; van Maarseveen, N.M.; Nijhuis, M. Fifteen years of HIV Protease Inhibitors: raising the barrier to resistance. Antiviral Res., 2010, 85(1), 59-74.
[] [PMID: 19853627]
Sangenito, L.S.; Gonçalves, D.S.; Seabra, S.H.; d’Avila-Levy, C.M.; Santos, A.L.S.; Branquinha, M.H. HIV aspartic peptidase inhibitors are effective drugs against the trypomastigote form of the human pathogen Trypanosoma cruzi. Int. J. Antimicrob. Agents, 2016, 48(4), 440-444.
[] [PMID: 27499433]
Silva, L.H.P.; Nussensweig, V. Sobre uma cepa de Trypanosoma cruzi altamente virulenta para o camundongo branco. Folia Clin. Biol. (Sao Paulo), 1953, 20, 191-207.
Sangenito, L.S.; de Guedes, A.A.; Gonçalves, D.S.; Seabra, S.H.; d’Avila-Levy, C.M.; Santos, A.L.S.; Branquinha, M.H. Deciphering the effects of nelfinavir and lopinavir on epimastigote forms of Trypanosoma cruzi. Parasitol. Int., 2017, 66(5), 529-536.
[] [PMID: 28377050]
Sangenito, L.S.; Menna-Barreto, R.F.S.; Oliveira, A.C.S.; d’Avila-Levy, C.M.; Branquinha, M.H.; Santos, A.L.S. Primary evidence of the mechanisms of action of HIV aspartyl peptidase inhibitors on Trypanosoma cruzi trypomastigote forms. Int. J. Antimicrob. Agents, 2018, 52(2), 185-194.
[] [PMID: 29635008]
Contreras, V.T.; Salles, J.M.; Thomas, N.; Morel, C.M.; Goldenberg, S. In vitro differentiation of Trypanosoma cruzi under chemically defined conditions. Mol. Biochem. Parasitol., 1985, 16(3), 315-327.
[] [PMID: 3903496]
De Souza, W. Growth and transformation of Trypanosoma cruzi.In: Handbook of Cell Proliferation; Briggs, A.P.; Coburn, J.A., Eds.; Nova Science, New York, USA, 2009.
Garcia, E.S.; Ratcliffe, N.A.; Whitten, M.M.; Gonzalez, M.S.; Azambuja, P. Exploring the role of insect host factors in the dynamics of Trypanosoma cruzi-Rhodnius prolixus interactions. J. Insect Physiol., 2007, 53(1), 11-21.
[] [PMID: 17141801]
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(1), 38-48.
[] [PMID: 15639138]
Pinho, R.T.; Beltramini, L.M.; Alves, C.R.; De-Simone, S.G. Trypanosoma cruzi: isolation and characterization of aspartyl proteases. Exp. Parasitol., 2009, 122(2), 128-133.
[] [PMID: 19217906]
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(5733), 409-415.
[] [PMID: 16020725]
Santos, L.O.; Garcia-Gomes, A.S.; Catanho, M.; Sodre, C.L.; Santos, A.L.S.; Branquinha, M.H.; d’Avila-Levy, C.M. Aspartic peptidases of human pathogenic trypanosomatids: perspectives and trends for chemotherapy. Curr. Med. Chem., 2013, 20(25), 3116-3133.
[] [PMID: 23298141]
Valdivieso, E.; Dagger, F.; Rascón, A. Leishmania mexicana: identification and characterization of an aspartyl proteinase activity. Exp. Parasitol., 2007, 116(1), 77-82.
[] [PMID: 17126324]
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.; d’Avila-Levy, C.M. HIV aspartyl peptidase inhibitors interfere with cellular proliferation, ultrastructure and macrophage infection of Leishmania amazonensis. PLoS One, 2009, 4(3)e4918
[] [PMID: 19325703]
Valdivieso, E.; Rangel, A.; Moreno, J.; Saugar, J.M.; Cañavate, C.; Alvar, J.; Dagger, F. Effects of HIV aspartyl-proteinase inhibitors on Leishmania sp. Exp. Parasitol., 2010, 126(4), 557-563.
[] [PMID: 20566367]
Santos, L.O.; Vitório, B.S.; Branquinha, M.H.; Pedroso e Silva, C.M.; Santos, A.L.S.; d’Avila-Levy, C.M. Nelfinavir is effective in inhibiting the multiplication and aspartic peptidase activity of Leishmania species, including strains obtained from HIV-positive patients. J. Antimicrob. Chemother., 2013, 68(2), 348-353.
[] [PMID: 23109184]
André. P.; Groettrup, M.; Klenerman, P.; De Giuli, R.; Booth, B.L.JR.; Cerundolo, V.; Bonneville, M.; Jotereau, F.; Zinkernagel, R.M.; Lotteau, V. An inhibitor of HIV-1 protease modulates proteasome activity, antigen presentation, and T cell responses. Proc. Natl. Acad. Sci. USA, 1998, 95, 13120-13124.
Pajonk, F.; Himmelsbach, J.; Riess, K.; Sommer, A.; McBride, W.H. The human immunodeficiency virus (HIV)-1 protease inhibitor saquinavir inhibits proteasome function and causes apoptosis and radiosensitization in non-HIV-associated human cancer cells. Cancer Res., 2002, 62(18), 5230-5235.
[PMID: 12234989]
Piccinini, M.; Rinaudo, M.T.; Anselmino, A.; Buccinnà, B.; Ramondetti, C.; Dematteis, A.; Ricotti, E.; Palmisano, L.; Mostert, M.; Tovo, P.A. The HIV protease inhibitors nelfinavir and saquinavir, but not a variety of HIV reverse transcriptase inhibitors, adversely affect human proteasome function. Antivir. Ther. (Lond.), 2005, 10(2), 215-223.
[PMID: 15865215]
De Barros, S.; Zakaroff-Girard, A.; Lafontan, M.; Galitzky, J.; Bourlier, V. Inhibition of human preadipocyte proteasomal activity by HIV protease inhibitors or specific inhibitor lactacystin leads to a defect in adipogenesis, which involves matrix metalloproteinase-9. J. Pharmacol. Exp. Ther., 2007, 320(1), 291-299.
[] [PMID: 17038510]
Reyskens, K.M.; Essop, M.F. HIV protease inhibitors and onset of cardiovascular diseases: a central role for oxidative stress and dysregulation of the ubiquitin-proteasome system. Biochim. Biophys. Acta, 2014, 1842(2), 256-268.
[] [PMID: 24275553]
Rubin, D.M.; Finley, D. Proteolysis. The proteasome: a protein-degrading organelle? Curr. Biol., 1995, 5(8), 854-858.
[] [PMID: 7583140]
Schubert, U.; Antón, L.C.; Gibbs, J.; Norbury, C.C.; Yewdell, J.W.; Bennink, J.R. Rapid degradation of a large fraction of newly synthesized proteins by proteasomes. Nature, 2000, 404(6779), 770-774.
[] [PMID: 10783891]
Kisselev, A.F.; Goldberg, A.L. Proteasome inhibitors: from research tools to drug candidates. Chem. Biol., 2001, 8(8), 739-758.
[] [PMID: 11514224]
González, J.; Ramalho-Pinto, F.J.; Frevert, U.; Ghiso, J.; Tomlinson, S.; Scharfstein, J.; Corey, E.J.; Nussenzweig, V. Proteasome activity is required for the stage-specific transformation of a protozoan parasite. J. Exp. Med., 1996, 184(5), 1909-1918.
[] [PMID: 8920878]
Cardoso, J.; Soares, M.J.; Menna-Barreto, R.F.S.; Le Bloas, R.; Sotomaior, V.; Goldenberg, S.; Krieger, M.A. Inhibition of proteasome activity blocks Trypanosoma cruzi growth and metacyclogenesis. Parasitol. Res., 2008, 103(4), 941-951.
[] [PMID: 18581141]
Branquinha, M.H.; Oliveira, S.S.; Sangenito, L.S.; Sodre, C.L.; Kneipp, L.F.; d’Avila-Levy, C.M.; Santos, A.L. Cruzipain: an update on its potential as chemotherapy target against the human pathogen Trypanosoma cruzi. Curr. Med. Chem., 2015, 22(18), 2225-2235.
[] [PMID: 25994861]
Campo, V.L.; Martins-Teixeira, M.B.; Carvalho, I. Trypanosoma cruzi invasion into host cells: a complex molecular targets interplay. Mini Rev. Med. Chem., 2016, 16(13), 1084-1097.
[] [PMID: 27281167]
Watanabe Costa, R.; da Silveira, J.F.; Bahia, D. Interactions between Trypanosoma cruzi secreted proteins and host cell signaling pathways. Front. Microbiol., 2016, 7, 388.
[] [PMID: 27065960]
Santa-Rita, R.M.; Barbosa, H.S.; de Castro, S.L. Ultrastructural analysis of edelfosine-treated trypomastigotes and amastigotes of Trypanosoma cruzi. Parasitol. Res., 2006, 100(1), 187-190.
[] [PMID: 16855821]
Sangenito, L.S.; Ennes-Vidal, V.; Marinho, F.A.; Da Mota, F.F.; Santos, A.L.S.; D’Avila-Levy, C.M.; Branquinha, M.H. Arrested growth of Trypanosoma cruzi by the calpain inhibitor MDL28170 and detection of calpain homologues in epimastigote forms. Parasitology, 2009, 136(4), 433-441.
[] [PMID: 19250597]
Díaz-Chiguer, D.L.; Hernández-Luis, F.; Nogueda-Torres, B.; Castillo, R.; Reynoso-Ducoing, O.; Hernández-Campos, A.; Ambrosio, J.R. JVG9, a benzimidazole derivative, alters the surface and cytoskeleton of Trypanosoma cruzi bloodstream trypomastigotes. Mem. Inst. Oswaldo Cruz, 2014, 109(6), 757-760.
[] [PMID: 25317703]
Santos, A.L.S.; d’Avila-Levy, C.M.; Dias, F.A.; Ribeiro, R.O.; Pereira, F.M.; Elias, C.G.; Souto-Padrón, T.; Lopes, A.H.; Alviano, C.S.; Branquinha, M.H.; Soares, R.M. Phytomonas serpens: cysteine peptidase inhibitors interfere with growth, ultrastructure and host adhesion. Int. J. Parasitol., 2006, 36(1), 47-56.
[] [PMID: 16310789]
Yorimitsu, T.; Klionsky, D.J. Eating the endoplasmic reticulum: quality control by autophagy. Trends Cell Biol., 2007, 17(6), 279-285.
[] [PMID: 17481899]
Duszenko, M.; Ginger, M.L.; Brennand, A.; Gualdrón-López, M.; Colombo, M.I.; Coombs, G.H.; Coppens, I.; Jayabalasingham, B.; Langsley, G.; de Castro, S.L.; Menna-Barreto, R.; Mottram, J.C.; Navarro, M.; Rigden, D.J.; Romano, P.S.; Stoka, V.; Turk, B.; Michels, P.A. Autophagy in protists. Autophagy, 2011, 7(2), 127-158.
[] [PMID: 20962583]
Raemaekers, T.; Esselens, C.; Annaert, W. Presenilin 1: more than just gamma-secretase. Biochem. Soc. Trans., 2005, 33(Pt 4), 559-562.
[] [PMID: 16042544]
Bezprozvanny, I. Presenilins: a novel link between intracellular calcium signaling and lysosomal function? J. Cell Biol., 2012, 198(1), 7-10.
[] [PMID: 22778275]
Koltai, T. Nelfinavir and other protease inhibitors in cancer: mechanisms involved in anticancer activity. F1000 Res., 2015, 4, 9.
[] [PMID: 26097685]
Dunn, W.A. Jr. Autophagy and related mechanisms of lysosome-mediated protein degradation. Trends Cell Biol., 1994, 4(4), 139-143.
[] [PMID: 14731737]
González-Polo, R.A.; Boya, P.; Pauleau, A.L.; Jalil, A.; Larochette, N.; Souquère, S.; Eskelinen, E.L.; Pierron, G.; Saftig, P.; Kroemer, G. The apoptosis/autophagy paradox: autophagic vacuolization before apoptotic death. J. Cell Sci., 2005, 118(Pt 14), 3091-3102.
[] [PMID: 15985464]
Touzet, O.; Philips, A. Resveratrol protects against protease inhibitor-induced reactive oxygen species production, reticulum stress and lipid raft perturbation. AIDS, 2010, 24(10), 1437-1447.
[] [PMID: 20539089]
Taura, M.; Kariya, R.; Kudo, E.; Goto, H.; Iwawaki, T.; Amano, M.; Suico, M.A.; Kai, H.; Mitsuya, H.; Okada, S. Comparative analysis of ER stress response into HIV protease inhibitors: lopinavir but not darunavir induces potent ER stress response via ROS/JNK pathway. Free Radic. Biol. Med., 2013, 65, 778-788.
[] [PMID: 23973637]
Falutz, J. Management of fat accumulation in patients with HIV infection. Curr. HIV/AIDS Rep., 2011, 8(3), 200-208.
[] [PMID: 21739217]
Estrada, V.; Portilla, J. Dyslipidemia related to antiretroviral therapy. AIDS Rev., 2011, 13(1), 49-56.
[PMID: 21412389]
Capel, E.; Auclair, M.; Caron-Debarle, M.; Capeau, J. Effects of ritonavir-boosted darunavir, atazanavir and lopinavir on adipose functions and insulin sensitivity in murine and human adipocytes. Antivir. Ther. (Lond.), 2012, 17(3), 549-556.
[] [PMID: 22293506]
Mori, K.; Ogawa, N.; Kawahara, T.; Yanagi, H.; Yura, T. mRNA splicing-mediated C-terminal replacement of transcription factor Hac1p is required for efficient activation of the unfolded protein response. Proc. Natl. Acad. Sci. USA, 2000, 97(9), 4660-4665.
[] [PMID: 10781071]
Parker, R.A.; Flint, O.P.; Mulvey, R.; Elosua, C.; Wang, F.; Fenderson, W.; Wang, S.; Yang, W.P.; Noor, M.A. Endoplasmic reticulum stress links dyslipidemia to inhibition of proteasome activity and glucose transport by HIV protease inhibitors. Mol. Pharmacol., 2005, 67(6), 1909-1919.
[] [PMID: 15755908]
Zha, B.S.; Wan, X.; Zhang, X.; Zha, W.; Zhou, J.; Wabitsch, M.; Wang, G.; Lyall, V.; Hylemon, P.B.; Zhou, H. HIV protease inhibitors disrupt lipid metabolism by activating endoplasmic reticulum stress and inhibiting autophagy activity in adipocytes. PLoS One, 2013, 8(3)e59514
[] [PMID: 23533630]
Riddle, T.M.; Kuhel, D.G.; Woollett, L.A.; Fichtenbaum, C.J.; Hui, D.Y. HIV protease inhibitor induces fatty acid and sterol biosynthesis in liver and adipose tissues due to the accumulation of activated sterol regulatory element-binding proteins in the nucleus. J. Biol. Chem., 2001, 276(40), 37514-37519.
[] [PMID: 11546771]
Williams, K.; Rao, Y.P.; Natarajan, R.; Pandak, W.M.; Hylemon, P.B. Indinavir alters sterol and fatty acid homeostatic mechanisms in primary rat hepatocytes by increasing levels of activated sterol regulatory element-binding proteins and decreasing cholesterol 7alpha-hydroxylase mRNA levels. Biochem. Pharmacol., 2004, 67(2), 255-267.
[] [PMID: 14698038]
Zhou, H.; Pandak, W.M., Jr; Lyall, V.; Natarajan, R.; Hylemon, P.B. HIV protease inhibitors activate the unfolded protein response in macrophages: implication for atherosclerosis and cardiovascular disease. Mol. Pharmacol., 2005, 68(3), 690-700.
[] [PMID: 15976036]
Zhou, H.; Gurley, E.C.; Jarujaron, S.; Ding, H.; Fang, Y.; Xu, Z.; Pandak, W.M., Jr; Hylemon, P.B. HIV protease inhibitors activate the unfolded protein response and disrupt lipid metabolism in primary hepatocytes. Am. J. Physiol. Gastrointest. Liver Physiol., 2006, 291(6), 1071-1080.
[] [PMID: 16861219]
Coffinier, C.; Hudon, S.E.; Farber, E.A.; Chang, S.Y.; Hrycyna, C.A.; Young, S.G.; Fong, L.G. HIV protease inhibitors block the zinc metalloproteinase ZMPSTE24 and lead to an accumulation of prelamin A in cells. Proc. Natl. Acad. Sci. USA, 2007, 104(33), 13432-13437.
[] [PMID: 17652517]
Clarke, S.G. HIV protease inhibitors and nuclear lamin processing: getting the right bells and whistles. Proc. Natl. Acad. Sci. USA, 2007, 104(35), 13857-13858.
[] [PMID: 17709742]
Goulbourne, C.N.; Vaux, D.J. HIV protease inhibitors inhibit FACE1/ZMPSTE24: a mechanism for acquired lipodystrophy in patients on highly active antiretroviral therapy? Biochem. Soc. Trans., 2010, 38(Pt 1), 292-296.
[] [PMID: 20074077]
Bociąga-Jasik, M.; Polus, A.; Góralska, J.; Czech, U.; Gruca, A.; Śliwa, A.; Garlicki, A.; Mach, T.; Dembińska-Kieć, A. Metabolic effects of the HIV protease inhibitor--saquinavir in differentiating human preadipocytes. Pharmacol. Rep., 2013, 65(4), 937-950.
[] [PMID: 24145088]
Menna-Barreto, R.F.; Salomão, K.; Dantas, A.P.; Santa-Rita, R.M.; Soares, M.J.; Barbosa, H.S.; de Castro, S.L. Different cell death pathways induced by drugs in Trypanosoma cruzi: an ultrastructural study. Micron, 2009, 40(2), 157-168.
[] [PMID: 18849169]
Fidalgo, L.M.; Gille, L. Mitochondria and trypanosomatids: targets and drugs. Pharm. Res., 2011, 28(11), 2758-2770.
[] [PMID: 21935742]
Menna-Barreto, R.F.; de Castro, S.L. The double-edged sword in pathogenic trypanosomatids: the pivotal role of mitochondria in oxidative stress and bioenergetics. BioMed Res. Int., 2014, 2014614014
[] [PMID: 24800243]
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(3)e642
[] [PMID: 20361030]
Kumar, P.; Lodge, R.; Raymond, F.; Ritt, J.F.; Jalaguier, P.; Corbeil, J.; Ouellette, M.; Tremblay, M.J. Gene expression modulation and the molecular mechanisms involved in Nelfinavir resistance in Leishmania donovani axenic amastigotes. Mol. Microbiol., 2013, 89(3), 565-582.
[] [PMID: 23782314]
Chandra, S.; Mondal, D.; Agrawal, K.C. HIV-1 protease inhibitor induced oxidative stress suppresses glucose stimulated insulin release: protection with thymoquinone. Exp. Biol. Med. (Maywood), 2009, 234(4), 442-453.
[] [PMID: 19234050]
Tricarico, P.M.; de Oliveira Franca, R.F.; Pacor, S.; Ceglia, V.; Crovella, S.; Celsi, F. HIV protease inhibitors apoptotic effect in SH-SY5Y neuronal cell line. Cell. Physiol. Biochem., 2016, 39(4), 1463-1470.
[] [PMID: 27607424]
Bissinger, R.; Waibel, S.; Bouguerra, G.; Al Mamun Bhuyan, A.; Abbès, S.; Lang, F.; Lang, F. Enhanced eryptosis following exposure to lopinavir. Cell. Physiol. Biochem., 2015, 37(6), 2486-2495.
[] [PMID: 26681533]
Bissinger, R.; Waibel, S.; Lang, F. Induction of suicidal erythrocyte death by nelfinavir. Toxins (Basel), 2015, 7(5), 1616-1628.
[] [PMID: 26008229]
Mondal, D.; Pradhan, L.; Ali, M.; Agrawal, K.C. HAART drugs induce oxidative stress in human endothelial cells and increase endothelial recruitment of mononuclear cells: exacerbation by inflammatory cytokines and amelioration by antioxidants. Cardiovasc. Toxicol., 2004, 4(3), 287-302.
[] [PMID: 15470276]
He, Z.; Chen, L.; You, J.; Qin, L.; Chen, X. Antiretroviral protease inhibitors potentiate chloroquine antimalarial activity in malaria parasites by regulating intracellular glutathione metabolism. Exp. Parasitol., 2009, 123(2), 122-127.
[] [PMID: 19538959]
Salomão, K.; De Santana, N.A.; Molina, M.T.; De Castro, S.L.; Menna-Barreto, R.F. Trypanosoma cruzi mitochondrial swelling and membrane potential collapse as primary evidence of the mode of action of naphthoquinone analogues. BMC Microbiol., 2013, 13, 196.
[] [PMID: 24004461]
Proto, W.R.; Coombs, G.H.; Mottram, J.C. Cell death in parasitic protozoa: regulated or incidental? Nat. Rev. Microbiol., 2013, 11(1), 58-66.
[] [PMID: 23202528]
Gills, J.J.; Lopiccolo, J.; Tsurutani, J.; Shoemaker, R.H.; Best, C.J.; Abu-Asab, M.S.; Borojerdi, J.; Warfel, N.A.; Gardner, E.R.; Danish, M.; Hollander, M.C.; Kawabata, S.; Tsokos, M.; Figg, W.D.; Steeg, P.S.; Dennis, P.A. Nelfinavir, a lead HIV protease inhibitor, is a broad-spectrum, anticancer agent that induces endoplasmic reticulum stress, autophagy, and apoptosis in vitro and in vivo. Clin. Cancer Res., 2007, 13(17), 5183-5194.
[] [PMID: 17785575]
Vincent, S.; Tourniaire, F.; El Yazidi, C.M.; Compe, E.; Manches, O.; Plannels, R.; Roche, R. Nelfinavir induces necrosis of 3T3F44-2A adipocytes by oxidative stress. J. Acquir. Immune Defic. Syndr., 2004, 37(5), 1556-1562.
[] [PMID: 15577407]
Yao, C. Major surface protease of trypanosomatids: one size fits all? Infect. Immun., 2010, 78(1), 22-31.
[] [PMID: 19858295]
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(1), 195-206.
[] [PMID: 21621652]
Ma, L.; Chen, K.; Meng, Q.; Liu, Q.; Tang, P.; Hu, S.; Yu, J. An evolutionary analysis of trypanosomatid GP63 proteases. Parasitol. Res., 2011, 109(4), 1075-1084.
[] [PMID: 21503641]
Osorio, L.; Ríos, I.; Gutiérrez, B.; González, J. Virulence factors of Trypanosoma cruzi: who is who? Microbes Infect., 2012, 14(15), 1390-1402.
[] [PMID: 23006853]
Romano, P.S.; Cueto, J.A.; Casassa, A.F.; Vanrell, M.C.; Gottlieb, R.A.; Colombo, M.I. Molecular and cellular mechanisms involved in the Trypanosoma cruzi/host cell interplay. IUBMB Life, 2012, 64(5), 387-396.
[] [PMID: 22454195]
Giorgi, M.E.; de Lederkremer, R.M. Trans-sialidase and mucins of Trypanosoma cruzi: an important interplay for the parasite. Carbohydr. Res., 2011, 346(12), 1389-1393.
[] [PMID: 21645882]
Soares, R.P.; Torrecilhas, A.C.; Assis, R.R.; Rocha, M.N.; Moura e Castro, F.A.; Freitas, G.F.; Murta, S.M.; Santos, S.L.; Marques, A.F.; Almeida, I.C.; Romanha, A.J. Intraspecies variation in Trypanosoma cruzi GPI-mucins: biological activities and differential expression of α-galactosyl residues. Am. J. Trop. Med. Hyg., 2012, 87(1), 87-96.
[] [PMID: 22764297]
Miller, B.R., III; Roitberg, A.E. Trypanosoma cruzi trans-sialidase as a drug target against Chagas disease (American trypanosomiasis). Future Med. Chem., 2013, 5(15), 1889-1900.
[] [PMID: 24144418]
Kashif, M.; Moreno-Herrera, A.; Villalobos-Rocha, J.C.; Nogueda-Torres, B.; Pérez-Villanueva, J.; Rodríguez-Villar, K.; Medina-Franco, J.L.; de Andrade, P.; Carvalho, I.; Rivera, G. Benzoic acid derivatives with trypanocidal activity: enzymatic analysis and molecular docking studies toward trans-sialidase. Molecules, 2017, 22(11)E1863
[] [PMID: 29084172]
Andrews, N.W.; Colli, W. Adhesion and interiorization of Trypanosoma cruzi in mammalian cells. J. Protozool., 1982, 29(2), 264-269.
[] [PMID: 7047731]
Sangenito, L.S.; d’Avila-Levy, C.M.; Branquinha, M.H.; Santos, A.L.S. Nelfinavir and lopinavir impair Trypanosoma cruzi trypomastigote infection in mammalian host cells and show anti-amastigote activity. Int. J. Antimicrob. Agents, 2016, 48(6), 703-711.
[] [PMID: 27838277]
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(9), 1292-1299.
[] [PMID: 18816190]
Brunet, L.R. Nitric oxide in parasitic infections. Int. Immunopharmacol., 2001, 1(8), 1457-1467.
[] [PMID: 11515811]
Alves, É.A.R.; de Miranda, M.G.; Borges, T.K.; Magalhães, K.G.; Muniz-Junqueira, M.I. Anti-HIV drugs, lopinavir/ritonavir and atazanavir, modulate innate immune response triggered by Leishmania in macrophages: the role of NF-κB and PPAR-γ. Int. Immunopharmacol., 2015, 24(2), 314-324.
[] [PMID: 25545854]
Lagathu, C.; Eustace, B.; Prot, M.; Frantz, D.; Gu, Y.; Bastard, J.P.; Maachi, M.; Azoulay, S.; Briggs, M.; Caron, M.; Capeau, J. Some HIV antiretrovirals increase oxidative stress and alter chemokine, cytokine or adiponectin production in human adipocytes and macrophages. Antivir. Ther. (Lond.), 2007, 12(4), 489-500.
[PMID: 17668557]
Estrela, R.C.; Ribeiro, F.S.; Seixas, B.V.; Suarez-Kurtz, G. Determination of lopinavir and ritonavir in blood plasma, seminal plasma, saliva and plasma ultra-filtrate by liquid chromatography/tandem mass spectrometry detection. Rapid Commun. Mass Spectrom., 2008, 22(5), 657-664.
[] [PMID: 18257112]
Pozio, E.; Morales, M.A.G. The impact of HIV-protease inhibitors on opportunistic parasites. Trends Parasitol., 2005, 21(2), 58-63.
[] [PMID: 15664527]
Alvar, J.; Aparicio, P.; Aseffa, A.; Den Boer, 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. Clin. Microbiol. Rev., 2008, 21(2), 334-359.
[] [PMID: 18400800]
Gramiccia, M.; Scalone, A.; Di Muccio, T.; Orsini, S.; Fiorentino, E.; Gradoni, L. The burden of visceral leishmaniasis in Italy from 1982 to 2012: a retrospective analysis of the multi-annual epidemic that occurred from 1989 to 2009. Euro Surveill., 2013, 18(29), 20535.
[] [PMID: 23929120]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy