Leishmaniasis: Current treatment and prospects for new drugs and vaccines

Current Medicinal Chemistry

Volumn 16, Issue 5, 2009, Pages 599-614

  Kedzierski, Lukasz ^a   Sakthianandeswaren, Anuratha ^a   Curtis, Joan M ^a   Andrews, Philip C ^b   Junk, Peter C ^c   Kedzierska, Katherine ^b  

^a WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH   (Australia)

^b UNIVERSITY OF MELBOURNE   (Australia)

^c MONASH UNIVERSITY   (Australia)

Author keywords

Antileishmanial drugs; Antileishmanial vaccine; Chemotherapy; Drug target; Immunology; Leishmaniasis

Indexed keywords

AMPHOTERICIN B; AMPHOTERICIN B CHOLESTEROL SULFATE; AMPHOTERICIN B LIPID COMPLEX; ANTILEISHMANIAL AGENT; CECROPIN A; FLUCONAZOLE; IMIQUIMOD; INDOLICIDIN; ITRACONAZOLE; KETOCONAZOLE; LEISHMANIA VACCINE; MAESABALIDE III; MAGAININ 2; MEGLUMINE ANTIMONATE; MELITTIN; MILTEFOSINE; PAROMOMYCIN; PENTAMIDINE; PLANT EXTRACT; POLYPEPTIDE ANTIBIOTIC AGENT; POSACONAZOLE; RESVERATROL; SAPONIN DERIVATIVE; SITAMAQUINE; STIBOGLUCONATE SODIUM; UNCLASSIFIED DRUG; ANTIPROTOZOAL AGENT; PROTOZOAL VACCINE;

ACTINIC KERATOSIS; ACUTE PANCREATITIS; AMINOTRANSFERASE BLOOD LEVEL; ANAPHYLAXIS; BASAL CELL CARCINOMA; BURNING SENSATION; CARDIOTOXICITY; CHILL; CLINICAL TRIAL; CONDYLOMA ACUMINATUM; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DIABETES MELLITUS; DRUG EFFICACY; DRUG FEVER; DRUG SAFETY; DRUG STRUCTURE; DRUG TARGETING; GASTROINTESTINAL DISEASE; HEART ARRHYTHMIA; HUMAN; HYPOKALEMIA; HYPOTENSION; IMMUNE RESPONSE; IMMUNOGENICITY; INFECTION CONTROL; INFLAMMATION; INJECTION SITE ABSCESS; INJECTION SITE DISCOMFORT; INJECTION SITE NECROSIS; INJECTION SITE PAIN; KIDNEY FAILURE; LEISHMANIA BRAZILIENSIS; LEISHMANIA INFANTUM; LEISHMANIA MAJOR; LEISHMANIA PANAMENSIS; LEISHMANIASIS; LIVER TOXICITY; MYALGIA; NEPHROTOXICITY; NONHUMAN; OTOTOXICITY; PATIENT COMPLIANCE; REVIEW; RIGOR; SIDE EFFECT; SINGLE DRUG DOSE; SKIN LEISHMANIASIS; VISCERAL LEISHMANIASIS;

ANTIPROTOZOAL AGENTS; HUMANS; LEISHMANIASIS; PROTOZOAN VACCINES;

EID: 63149112758     PISSN: 09298673     EISSN: None     Source Type: Journal    
DOI: 10.2174/092986709787458489     Document Type: Review

References (214)

1. Handman, E. Cell biology of Leishmania. Adv. Parasitol., 1999, 44, 1-39.
2. Chevalier, B.; Carmoi, T.; Sagui, E.; Carrette, P.; Petit, D.; De Mauleon, P.; Pourriere, M.; Martinie, C.; Didier, C. Report of the first cases of cutaneous leishmaniasis in East Timor. Clin. Infect. Dis., 2000, 30, 840.
3. Kongkaew, W.; Siriarayaporn, P.; Leelayoova, S.; Supparatpinyo, K.; Areechokchai, D.; Duang-ngern, P.; Chanachai, K.; Sukmee, T.; Samung, Y.; Sridurongkathum, P. Autochthonous visceral leishmaniasis: A report of a second case in Thailand. Southeast Asian J. Trop. Med. Public Health, 2007, 38, 8-12.
4. Rose, K.; Curtis, J.; Baldwin, T.; Mathis, A.; Kumar, B.; Sakthianandeswaren, A.; Spurck, T.; Low Choy, J.; Handman, E. Cutaneous leishmaniasis in red kangaroos: Isolation and characterisation of the causative organisms. Int. J. Parasitol., 2004, 34, 655-664.
5. WHO Initiative for Vaccine Research. http://www.who.int/vaccine_ research/diseases/soa_parasitic/en/index3.html
6. Cruz, I.; Nieto, J.; Moreno, J.; Canavate, C.; Desjeux, P.; Alvar, J. Leishmania/HIV co-infections in the second decade. Indian J. Med. Res., 2006, 123, 357-388.
7. Reithinger, R.; Mohsen, M.; Aadil, K.; Sidiqi, M.; Erasmus, P.; Coleman, P.G. Anthroponotic cutaneous leishmaniasis, Kabul, Afghanistan. Emerg. Infect. Dis., 2003, 9, 727-729.
8. Coleman, R.E.; Burkett, D.A.; Putnam, J.L.; Sherwood, V.; Caci, J.B.; Jennings, B.T.; Hochberg, L.P.; Spradling, S.L.; Rowton, E.D.; Blount, K.; Ploch, J.; Hopkins, G.; Raymond, J.L.; O'Guinn, M.L.; Lee, J.S.; Weina, P.J. Impact of phlebotomine sand flies on U.S. Military operations at Tallil Air Base, Iraq: 1. background, military situation, and development of a "Leishmaniasis Control Program". J. Med. Entomol., 2006, 43, 647-662.
9. Reiner, S.L.; Locksley, R.M. The regulation of immunity to Leishmania major. Ann. Rev. Immunol., 1995, 13, 151-177.
10. Ahuja, S.S.; Reddick, R.L.; Sato, N.; Montalbo, E.; Kostecki, V.; Zhao, W.; Dolan, M.J.; Melby, P.C.; Ahuja, S.K. Dendritic cell (DC)-based anti-infective strategies: DCs engineered to secrete IL12 are a potent vaccine in a murine model of an intracellular infection. J. Immunol., 1999, 163, 3890-3897.
11. Belkaid, Y.; Mendez, S.; Lira, R.; Kadambi, N.; Milon, G.; Sacks, D. A natural model of Leishmania major infection reveals a prolonged "silent" phase of parasite amplification in the skin before the onset of lesion formation and immunity. J. Immunol., 2000, 165, 969-977.
12. McFarlane, E.; Perez, C.; Charmoy, M.; Allenbach, C.; Carter, K.C.; Alexander, J.; Tacchini-Cottier, F. Neutrophils contribute to development of a protective immune response during onset of infection with Leishmania donovani. Infect. Immun., 2008, 76, 532-541.
13. Laskay, T.; van Zandbergen, G.; Solbach, W. Neutrophil granulocytes as host cells and transport vehicles for intracellular pathogens: Apoptosis as infection-promoting factor. Immunobiology, 2008, 213, 183-191.
14. Gorak, P.M.; Engwerda, C.R.; Kaye, P.M. Dendritic cells, but not macrophages, produce IL-12 immediately following Leishmania donovani infection. Eur. J. Immunol., 1998, 28, 687-695
15. von Stebut, E.; Belkaid, Y.; Jakob, T.; Sacks, D.L.; Udey, M.C. Uptake of Leishmania major amastigotes results in activation and interleukin 12 release from murine skin-derived dendritic cells: Implications for the initiation of anti-Leishmania immunity. J. Exp. Med., 1998, 188, 1547-1552.
16. Belkaid, Y.; Butcher, B.; Sacks, D.L. Analysis of cytokine production by inflammatory mouse macrophages at the single-cell level: Selective impairment of IL-12 induction in Leishmania-infected cells. Eur. J. Immunol., 1998, 28, 1389-1400.
17. Sacks, D.; Noben-Trauth, N. The immunology of susceptibility and resistance to Leishmania major in mice. Nat. Rev. Immunol., 2002, 2, 845-858.
18. Scott, P. The role of TH1 and TH2 cells in experimental cutaneous leishmaniasis. Exp. Parasitol., 1989, 68, 369-372
19. Bogdan, C.; Rollinghoff, M.; Diefenbach, A. The role of nitric oxide in innate immunity. Immunol. Rev., 2000, 173, 17-26
20. Moll, H.; Muller, C.; Gillitzer, R.; Fuchs, H.; Rollinghoff, M.; Simon, M.M.; Kramer, M.D. Expression of T-cell-associated serine proteinase 1 during murine Leishmania major infection correlates with susceptibility to disease. Infect. Immun., 1991, 59, 4701-4705
21. Uzonna, J.E.; Joyce, K.L.; Scott, P. Low dose Leishmania major promotes a transient T helper cell type 2 response that is downregulated by interferon gamma-producing CD8+ T cells. J. Exp. Med., 2004, 199, 1559-1566.
22. Sacks, D.L.; Scott, P.A.; Asofsky, R.; Sher, F.A. Cutaneous leishmaniasis in anti-IgM-treated mice: Enhanced resistance due to functional depletion of a B cell-dependent T cell involved in the suppressor pathway. J. Immunol., 1984, 132, 2072-2077.
23. Hoerauf, A.; Solbach, W.; Rollinghoff, M.; Gessner, A. Effect of IL-7 treatment on Leishmania major-infected BALB.Xid mice: Enhanced lymphopoiesis with sustained lack of B1 cells and clinical aggravation of disease. Int. Immunol., 1995, 7, 1879-1884.
24. Smelt, S.C.; Cotterell, S.E.; Engwerda, C.R.; Kaye, P.M. B celldeficient mice are highly resistant to Leishmania donovani infection, but develop neutrophil-mediated tissue pathology. J. Immunol., 2000, 164, 3681-3688.
25. Ronet, C.; Voigt, H.; Himmelrich, H.; Doucey, M.A.; Hauyon-La Torre, Y.; Revaz-Breton, M.; Tacchini-Cottier, F.; Bron, C.; Louis, J.; Launois, P. Leishmania major-specific B cells are necessary for Th2 cell development and susceptibility to L. major LV39 in BALB/c mice. J. Immunol., 2008, 180, 4825-4835.
26. Brown, D.R.; Reiner, S.L. Polarized helper-T-cell responses against Leishmania major in the absence of B cells. Infect. Immun., 1999, 67, 266-270.
27. von Stebut, E.; Udey, M.C. Requirements for Th1-dependent immunity against infection with Leishmania major. Microb. Infect., 2004, 6, 1102-1109.
28. Kopf, M.; Brombacher, F.; Kohler, G.; Kienzle, G.; Widmann, K.H.; Lefrang, K.; Humborg, C.; Ledermann, B.; Solbach, W. IL4- deficient Balb/ c mice resist infection with Leishmania major. J. Exp. Med., 1996, 184, 1127-1136.
29. Radwanska, M.; Cutler, A.J.; Hoving, J.C.; Magez, S.; Holscher, C.; Bohms, A.; Arendse, B.; Kirsch, R.; Hunig, T.; Alexander, J.; Kaye, P.; Brombacher, F. Deletion of IL-4Ralpha on CD4 T cells renders BALB/c mice resistant to Leishmania major infection. PLoS Pathogens, 2007, 3, e68.
30. Noben-Trauth, N.; Kropf, P.; Muller, I. Susceptibility to Leishmania major infection in interleukin-4-deficient mice. Science, 1996, 271, 987-990.
31. Mohrs, M.; Holscher, C.; Brombacher, F. Interleukin-4 receptor alpha-deficient BALB/c mice show an unimpaired T helper 2 polarization in response to Leishmania major infection. Infect. Immun., 2000, 68, 1773-1780.
32. Wang, Z.E.; Reiner, S.L.; Zheng, S.; Dalton, D.K.; Locksley, R.M. CD4+ effector cells default to the Th2 pathway in interferon gamma-deficient mice infected with Leishmania major. J. Exp. Med., 1994, 179, 1367-1371.
33. Swihart, K.; Fruth, U.; Messmer, N.; Hug, K.; Behin, R.; Huang, S.; Del Giudice, G.; Aguet, M.; Louis, J.A. Mice from a genetically resistant background lacking the interferon gamma receptor are susceptible to infection with Leishmania major but mount a polarized T helper cell 1-type CD4+ T cell response. J. Exp. Med., 1995, 181, 961-971.
34. Sadick, M.D.; Heinzel, F.P.; Holaday, B.J.; Pu, R.T.; Dawkins, R.S.; Locksley, R.M. Cure of murine leishmaniasis with antiinterleukin 4 monoclonal antibody. Evidence for a T celldependent, interferon gamma-independent mechanism. J. Exp. Med., 1990, 171, 115-127.
35. Anderson, C.F.; Mendez, S.; Sacks, D.L. Nonhealing infection despite Th1 polarization produced by a strain of Leishmania major in C57BL/6 mice. J. Immunol., 2005, 174, 2934-2941.
36. Belkaid, Y.; Hoffmann, K.F.; Mendez, S.; Kamhawi, S.; Udey, M.C.; Wynn, T.A.; Sacks, D.L. The role of interleukin (IL)-10 in the persistence of Leishmania major in the skin after healing and the therapeutic potential of anti-IL-10 receptor antibody for sterile cure. J. Exp. Med., 2001, 194, 1497-1506.
37. Murphy, M.L.; Wille, U.; Villegas, E.N.; Hunter, C.A.; Farrell, J.P. IL-10 mediates susceptibility to Leishmania donovani infection. Eur. J. Immunol., 2001, 31, 2848-2856.
38. Stober, C.B.; Lange, U.G.; Roberts, M.T.; Alcami, A.; Blackwell, J.M. IL-10 from regulatory T cells determines vaccine efficacy in murine Leishmania major infection. J. Immunol., 2005, 175, 2517-2524.
39. Silvestre, R.; Cordeiro-Da-Silva, A.; Santarem, N.; Vergnes, B.; Sereno, D.; Ouaissi, A. SIR2-deficient Leishmania infantum induces a defined IFN-gamma/IL-10 pattern that correlates with protection. J. Immunol., 2007, 179, 3161-3170.
40. Kedzierski, L.; Curtis, J.M.; Doherty, P.C.; Handman, E.; Kedzierska, K. Decreased IL-10 and IL-13 production and increased CD44hi T cell recruitment contribute to Leishmania major immunity induced by non-persistent parasites. Eur. J. Immunol., 2008, 38, 3090-3100.
41. Sypek, J.P.; Chung, C.L.; Mayor, S.E.; Subramanyam, J.M.; Goldman, S.J.; Sieburth, D.S.; Wolf, S.F.; Schaub, R.G. Resolution of cutaneous leishmaniasis: Interleukin 12 initiates a protective T helper type 1 immune response. J. Exp. Med., 1993, 177, 1797-1802.
42. Matthews, D.J.; Emson, C.L.; McKenzie, G.J.; Jolin, H.E.; Blackwell, J.M.; McKenzie, A.N. IL-13 is a susceptibility factor for Leishmania major infection. J. Immunol., 2000, 164, 1458-1462.
43. Kindler, V.; Sappino, A.P.; Grau, G.E.; Piguet, P.F.; Vassalli, P. The inducing role of tumor necrosis factor in the development of bactericidal granulomas during BCG infection. Cell, 1989, 56, 731-740.
44. Liew, F.Y.; Parkinson, C.; Millott, S.; Severn, A.; Carrier, M. Tumour necrosis factor (TNF alpha) in leishmaniasis. I. TNF alpha mediates host protection against cutaneous leishmaniasis. Immunology, 1990, 69, 570-573.
45. Titus, R.G.; Sherry, B.; Cerami, A. Tumor necrosis factor plays a protective role in experimental murine cutaneous leishmaniasis. J. Exp. Med., 1989, 170, 2097-2104.
46. Gumy, A.; Louis, J.A.; Launois, P. The murine model of infection with Leishmania major and its importance for the deciphering of mechanisms underlying differences in Th cell differentiation in mice from different genetic backgrounds. Int. J. Parasitol., 2004, 34, 433-444.
47. Ajdary, S.; Alimohammadian, M.H.; Eslami, M.B.; Kemp, K.; Kharazmi, A. Comparison of the immune profile of nonhealing cutaneous Leishmaniasis patients with those with active lesions and those who have recovered from infection. Infect. Immun., 2000, 68, 1760-1764.
48. Khalil, E.A.; Ayed, N.B.; Musa, A.M.; Ibrahim, M.E.; Mukhtar, M.M.; Zijlstra, E.E.; Elhassan, I.M.; Smith, P.G.; Kieny, P.M.; Ghalib, H.W.; Zicker, F.; Modabber, F.; Elhassan, A.M. Dichotomy of protective cellular immune responses to human visceral leishmaniasis. Clin. Exp. Immunol., 2005, 140, 349-353.
49. Kedzierski, L.; Zhu, Y.; Handman, E. Leishmania vaccines: Progress and problems. Parasitology, 2006, 133 (Suppl), S87-112.
50. Tabbara, K.S. Progress towards a Leishmania vaccine. Saudi Med. J., 2006, 27, 942-950.
51. Russo, D.M.; Burns, J.M. Jr.; Carvalho, E.M.; Armitage, R.J.; Grabstein, K.H.; Button, L.L.; McMaster, W.R.; Reed, S.G. Human T cell responses to gp63, a surface antigen of Leishmania. J. Immunol., 1991, 147, 3575-3580.
52. Nascimento, E.; Mayrink, W.; da Costa, C. A.; Michalick, M. S.; Melo, M. N.; Barros, G. C.; Dias, M.; Antunes, C. M.; Lima, M. S.; Taboada, D. C.; Liu, T.Y. Vaccination of humans against cutaneous leishmaniasis: cellular and humoral immune responses. Infect. Immun., 1990, 58, 2198-2203.
53. McMahon-Pratt, D.; Traub-Cseko, Y.; Lohman, K.L.; Rogers, D.D.; Beverley, S.M. Loss of the GP46/M-2 surface membrane glycoprotein gene family in the Leishmania braziliensis complex. Mol. Biochem. Parasitol., 1992, 50, 151-160.
54. Kedzierski, L.; Montgomery, J.; Bullen, D.; Curtis, J.; Gardiner, E.; Jimenez-Ruiz, A.; Handman, E. A leucine-rich repeat motif of Leishmania parasite surface antigen 2 binds to macrophages through the complement receptor 3. J. Immunol., 2004, 172, 4902-4906.
55. Handman, E.; Symons, F.M.; Baldwin, T.M.; Curtis, J.M.; Scheerlinck, J.P. Protective vaccination with promastigote surface antigen 2 from Leishmania major is mediated by a TH1 type of immune response. Infect. Immun., 1995, 63, 4261-4267.
56. Sjolander, A.; Baldwin, T.M.; Curtis, J.M.; Bengtsson, K.L.; Handman, E. Vaccination with recombinant Parasite Surface Antigen 2 from Leishmania major induces a Th1 type of immune response but does not protect against infection. Vaccine, 1998, 16, 2077-2084.
57. Sjolander, A.; Baldwin, T.M.; Curtis, J.M.; Handman, E. Induction of a Th1 immune response and simultaneous lack of activation of a Th2 response are required for generation of immunity to leishmaniasis. J. Immunol., 1998, 160, 3949-3957.
58. Handman, E.; Noormohammadi, A.H.; Curtis, J.M.; Baldwin, T.; Sjolander, A. Therapy of murine cutaneous leishmaniasis by DNA vaccination. Vaccine, 2000, 18, 3011-3017.
59. Champsi, J.; McMahon-Pratt, D. Membrane glycoprotein M-2 protects against Leishmania amazonensis infection. Infect. Immun., 1988, 56, 3272-3279.
60. Mougneau, E.; Altare, F.; Wakil, A.E.; Zheng, S.; Coppola, T.; Wang, Z.E.; Waldmann, R.; Locksley, R.M.; Glaichenhaus, N. Expression cloning of a protective Leishmania antigen. Science, 1995, 268, 563-566.
61. Launois, P.; Maillard, I.; Pingel, S.; Swihart, K.G.; Xenarios, I.; Acha-Orbea, H.; Diggelmann, H.; Locksley, R.M.; MacDonald, H.R.; Louis, J.A. IL-4 rapidly produced by V beta 4 V alpha 8 CD4+ T cells instructs Th2 development and susceptibility to Leishmania major in BALB/c mice. Immunity, 1997, 6, 541-549.
62. Julia, V.; Rassoulzadegan, M.; Glaichenhaus, N. Resistance to Leishmania major induced by tolerance to a single antigen. Science, 1996, 274, 421-423.
63. Melby, P.C.; Yang, J.; Zhao, W.; Perez, L.E.; Cheng, J. Leishmania donovani p36(LACK) DNA vaccine is highly immunogenic but not protective against experimental visceral leishmaniasis. Infect. Immun., 2001, 69, 4719-4725.
64. Rafati, S.; Nakhaee, A.; Taheri, T.; Taslimi, Y.; Darabi, H.; Eravani, D.; Sanos, S.; Kaye, P.; Taghikhani, M.; Jamshidi, S.; Rad, M.A. Protective vaccination against experimental canine visceral leishmaniasis using a combination of DNA and protein immunization with cysteine proteinases type I and II of L. infantum. Vaccine, 2005, 23, 3716-3725.
65. Soong, L.; Duboise, S.M.; Kima, P.; McMahon-Pratt, D. Leishmania pifanoi amastigote antigens protect mice against cutaneous leishmaniasis. Infect. Immun., 1995, 63, 3559-3566.
66. Basu, R.; Bhaumik, S.; Basu, J.M.; Naskar, K.; De, T.; Roy, S. Kinetoplastid membrane protein-11 DNA vaccination induces complete protection against both pentavalent antimonial-sensitive and -resistant strains of Leishmania donovani that correlates with inducible nitric oxide synthase activity and IL-4 generation: Evidence for mixed Th1- and Th2-like responses in visceral leishmaniasis. J. Immunol., 2005, 174, 7160-7171.
67. Streit, J.A.; Recker, T.J.; Donelson, J.E.; Wilson, M.E. BCG expressing LCR1 of Leishmania chagasi induces protective immunity in susceptible mice. Exp. Parasitol., 2000, 94, 33-41.
68. Stager, S.; Smith, D.F.; Kaye, P.M. Immunization with a recombinant stage-regulated surface protein from Leishmania donovani induces protection against visceral leishmaniasis. J. Immunol., 2000, 165, 7064-7071.
69. Tewary, P.; Jain, M.; Sahani, M.H.; Saxena, S.; Madhubala, R. A heterologous prime-boost vaccination regimen using ORFF DNA and recombinant ORFF protein confers protective immunity against experimental visceral leishmaniasis. J. Infect. Dis., 2005, 191, 2130-2137.
70. Iborra, S.; Soto, M.; Carrion, J.; Nieto, A.; Fernandez, E.; Alonso, C.; Requena, J.M. The Leishmania infantum acidic ribosomal protein P0 administered as a DNA vaccine confers protective immunity to Leishmania major infection in BALB/c mice. Infect. Immun., 2003, 71, 6562-6572.
71. Saravia, N.G.; Hazbon, M.H.; Osorio, Y.; Valderrama, L.; Walker, J.; Santrich, C.; Cortazar, T.; Lebowitz, J.H.; Travi, B.L. Protective immunogenicity of the paraflagellar rod protein 2 of Leishmania mexicana. Vaccine, 2005, 23, 984-995.
72. Aguilar-Be, I.; da Silva Zardo, R.; Paraguai de Souza, E.; Borja-Cabrera, G.P.; Rosado-Vallado, M.; Mut-Martin, M.; Garcia-Miss Mdel, R.; Palatnik de Sousa, C.B.; Dumonteil, E. Cross-protective efficacy of a prophylactic Leishmania donovani DNA vaccine against visceral and cutaneous murine leishmaniasis. Infect. Immun., 2005, 73, 812-819.
73. Coler, R.N.; Reed, S.G. Second-generation vaccines against leishmaniasis. Trends Parasitol., 2005, 21, 244-249.
74. Skeiky, Y.A.; Coler, R.N.; Brannon, M.; Stromberg, E.; Greeson, K.; Crane, R.T.; Webb, J.R.; Campos-Neto, A.; Reed, S.G. Protective efficacy of a tandemly linked, multi-subunit recombinant leishmanial vaccine (Leish-111f) formulated in MPL adjuvant. Vaccine, 2002, 20, 3292-3303.
75. Coler, R.N.; Goto, Y.; Bogatzki, L.; Raman, V.; Reed, S.G. Leish-111f, a recombinant polyprotein vaccine that protects against visceral Leishmaniasis by elicitation of CD4+ T cells. Infect. Immun., 2007, 75, 4648-4654.
76. Gradoni, L.; Foglia Manzillo, V.; Pagano, A.; Piantedosi, D.; De Luna, R.; Gramiccia, M.; Scalone, A.; Di Muccio, T.; Oliva, G. Failure of a multi-subunit recombinant leishmanial vaccine (MML) to protect dogs from Leishmania infantum infection and to prevent disease progression in infected animals. Vaccine, 2005, 23, 5245-5251
77. Uzonna, J.E.; Wei, G.; Yurkowski, D.; Bretscher, P. Immune elimination of Leishmania major in mice: Implications for immune memory, vaccination, and reactivation disease. J. Immunol., 2001, 167, 6967-6974.
78. Titus, R.G.; Gueiros-Filho, F.J.; de Freitas, L.A.; Beverley, S.M. Development of a safe live Leishmania vaccine line by gene replacement. Proc. Natl. Acad. Sci. USA, 1995, 92, 10267-10271.
79. 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, 6794-6801.
80. Uzonna, J.E.; Spath, G.F.; Beverley, S.M.; Scott, P. Vaccination with phosphoglycan-deficient Leishmania major protects highly susceptible mice from virulent challenge without inducing a strong Th1 response. J. Immunol., 2004, 172, 3793-3797.
81. Spath, G.F.; Lye, L.F.; Segawa, H.; Turco, S.J.; Beverley, S.M. Identification of a compensatory mutant (lpg2-REV) of Leishmania major able to survive as amastigotes within macrophages without LPG2-dependent glycoconjugates and its significance to virulence and immunization strategies. Infect. Immun., 2004, 72, 3622-3627
82. Selvapandiyan, A.; Debrabant, A.; Duncan, R.; Muller, J.; Salotra, P.; Sreenivas, G.; Salisbury, J.L.; Nakhasi, H.L. Centrin gene disruption impairs stage-specific basal body duplication and cell cycle progression in Leishmania. J. Biol. Chem., 2004, 279, 25703-25710.
83. Selvapandiyan, A.; Duncan, R.; Debrabant, A.; Lee, N.; Sreenivas, G.; Salotra, P.; Nakhasi, H.L. Genetically modified live attenuated parasites as vaccines for leishmaniasis. Indian J. Med. Res., 2006, 123, 455-466.
84. Khalil, E.A.; Musa, A.M.; Modabber, F.; El-Hassan, A.M. Safety and immunogenicity of a candidate vaccine for visceral leishmaniasis (Alum-precipitated autoclaved Leishmania major + BCG) in children: An extended phase II study. Ann. Trop. Paediatr., 2006, 26, 357-361.
85. Armijos, R.X.; Weigel, M.M.; Calvopina, M.; Hidalgo, A.; Cevallos, W.; Correa, J. Safety, immunogenecity, and efficacy of an autoclaved Leishmania amazonensis vaccine plus BCG adjuvant against New World cutaneous leishmaniasis. Vaccine, 2004, 22, 1320-1326.
86. Velez, I.D.; Gilchrist, K.; Arbelaez, M.P.; Rojas, C.A.; Puerta, J.A.; Antunes, C.M.; Zicker, F.; Modabber, F. Failure of a killed Leishmania amazonensis vaccine against American cutaneous leishmaniasis in Colombia. Trans. R. Soc. Trop. Med. Hyg., 2005, 99, 593-598.
87. Paul, Y. Polio Eradication: Let us face the facts and accept the reality. Indian Pediatr., 2005, 42, 728-729.
88. Croft, S.L.; Coombs, G.H. Leishmaniasis - current chemotherapy and recent advances in the search for novel drugs. Trends Parasitol., 2003, 19, 502-508.
89. Sundar, S.; More, D.K.; Singh, M.K.; Singh, V.P.; Sharma, S.; Makharia, A.; Kumar, P.C.; Murray, H.W. Failure of pentavalent antimony in visceral leishmaniasis in India: Report from the center of the Indian epidemic. Clin. Infect. Dis., 2000, 31, 1104-1107
90. Sundar, S. Drug resistance in Indian visceral leishmaniasis. Trop. Med. Int. Health, 2001, 6, 849-854.
91. Chappuis, F.; Sundar, S.; Hailu, A.; Ghalib, H.; Rijal, S.; Peeling, R.W.; Alvar, J.; Boelaert, M. Visceral leishmaniasis: What are the needs for diagnosis, treatment and control? Nat. Rev. Microbiol., 2007, 5, 873-882.
92. Roberts, W.L.; Berman, J.D.; Rainey, P.M. In vitro antileishmanial properties of tri- and pentavalent antimonial preparations. Antimicrob Agents Chemother., 1995, 39, 1234-1239
93. Ferreira Cdos, S.; Martins, P.S.; Demicheli, C.; Brochu, C.; Ouellette, M.; Frezard, F. Thiol-induced reduction of antimony(V) into antimony(III): A comparative study with trypanothione, cysteinyl-glycine, cysteine and glutathione. Biometals, 2003, 16, 441-446.
94. Cunningham, M.L.; Zvelebil, M.J.; Fairlamb, A.H. Mechanism of inhibition of trypanothione reductase and glutathione reductase by trivalent organic arsenicals. Eur. J. Biochem., 1994, 221, 285-295.
95. Wyllie, S.; Fairlamb, A.H. Differential toxicity of antimonial compounds and their effects on glutathione homeostasis in a human leukaemia monocyte cell line. Biochem. Pharmacol., 2006, 71, 257-267.
96. Sudhandiran, G.; Shaha, C. Antimonial-induced increase in intracellular Ca2+ through non-selective cation channels in the host and the parasite is responsible for apoptosis of intracellular Leishmania donovani amastigotes. J. Biol. Chem., 2003, 278, 25120-25132.
97. Roberts, W.L.; McMurray, W.J.; Rainey, P.M. Characterization of the antimonial antileishmanial agent meglumine antimonate (glucantime). Antimicrob. Agents Chemother., 1998, 42, 1076-1082
98. Frezard, F.; Martins, P.S.; Barbosa, M.C.; Pimenta, A.M.; Ferreira, W.A.; de Melo, J.E.; Mangrum, J.B.; Demicheli, C. New insights into the chemical structure and composition of the pentavalent antimonial drugs, meglumine antimonate and sodium stibogluconate. J. Inorg. Biochem., 2008, 102, 656-665.
99. Demicheli, C.; Ochoa, R.; da Silva, J.B.; Falcao, C.A.; Rossi-Bergmann, B.; de Melo, A.L.; Sinisterra, R.D.; Frezard, F. Oral delivery of meglumine antimoniate-beta-cyclodextrin complex for treatment of leishmaniasis. Antimicrob. Agents Chemother., 2004, 48, 100-103.
100. Martins, P.S.; Ochoa, R.; Pimenta, A.M.; Ferreira, L.A.; Melo, A.L.; da Silva, J.B.; Sinisterra, R.D.; Demicheli, C.; Frezard, F. Mode of action of beta-cyclodextrin as an absorption enhancer of the water-soluble drug meglumine antimoniate. Int. J. Pharm., 2006, 325, 39-47.
101. Demicheli, C.; Frezard, F.; Lecouvey, M.; Garnier-Suillerot, A. Antimony(V) complex formation with adenine nucleosides in aqueous solution. Biochim. Biophys. Acta, 2002, 1570, 192-198.
102. Marr, J.J. Purine analogs as chemotherapeutic agents in leishmaniasis and American trypanosomiasis. J. Lab. Clin. Med., 1991, 118, 111-119.
103. Burguera, J.L.; Burguera, M.; Petit de Pena, Y.; Lugo, A.; Anez, N. Selective determination of antimony (III) and antimony (IV) in serum and urine and of total antimony in skin biopsies of patients with entaneous Leishmaniasis treated with meglumine antimoniate. J. Trace Elem. Med. Biol., 1993, 10, 66-70.
104. Fairlamb, A.H.; Cerami, A. Metabolism and functions of trypanothione in the Kinetoplastida. Annu. Rev. Microbiol., 1992, 46, 695-729.
105. Denton, H.; McGregor, J.C.; Coombs, G.H. Reduction of anti-leishmanial pentavalent antimonial drugs by a parasite-specific thiol-dependent reductase, TDR1. Biochem. J., 2004, 381, 405-412
106. Fox, K.R.; Sansom, C.E.; Stevens, M.F. Footprinting studies on the, sequence-selective binding of pentamidine to DNA. FEBS Lett., 1990, 266, 150-154.
107. Antoniou, T.; Gough, K.A. Early-onset pentamidine-associated second-degree heart block and sinus bradycardia: Case report and review of the literature. Pharmacotherapy, 2005, 25, 899-903.
108. Assan, R.; Perronne, C.; Assan, D.; Chotard, L.; Mayaud, C.; Matheron, S.; Zucman, D. Pentamidine-induced derangements of glucose homeostasis. Determinant roles of renal failure and drug accumulation. A study of 128 patients. Diabetes Care, 1995, 18, 47-55.
109. Andersen, E.M.; Cruz-Saldarriaga, M.; Llanos-Cuentas, A.; Luz-Cjuno, M.; Echevarria, J.; Miranda-Verastegui, C.; Colina, O.; Berman, J.D. Comparison of meglumine antimoniate and pentamidine for peruvian cutaneous leishmaniasis. Am. J. Trop. Med. Hyg., 2005, 72, 133-137.
110. Bray, P.G.; Barrett, M.P.; Ward, S.A.; de Koning, H.P. Pentamidine uptake and resistance in pathogenic protozoa: Past, present and future. Trends Parasitol., 2003, 19, 232-239.
111. Saha, A.K.; Mukherjee, T.; Bhaduri, A. Mechanism of action of amphotericin B on Leishmania donovani promastigotes. Mol. Biochem. Parasitol., 1986, 19, 195-200.
112. Wasan, K.M.; Morton, R.E.; Rosenblum, M.G.; Lopez-Berestein, G. Decreased toxicity of liposomal amphotericin B due to association of amphotericin B with high-density lipoproteins: Role of lipid transfer protein. J. Pharm. Sci., 1994, 83, 1006-1010.
113. Murray, H.W. Progress in the treatment of a neglected infectious disease: Visceral leishmaniasis. Expert Rev. Anti. Infect. Ther., 2004, 2, 279-292.
114. Amato, V.S.; Rabello, A.; Rotondo-Silva, A.; Kono, A.; Maldonado, T.P.; Alves, I.C.; Floeter-Winter, L.M.; Neto, V.A.; Shikanai-Yasuda, M.A. Successful treatment of cutaneous leishmaniasis with lipid formulations of amphotericin B in two immunocompromised patients. Acta Trop., 2004, 92, 127-132.
115. Croft, S.L.; Engel, J. Miltefosine - discovery of the antileishmanial activity of phospholipid derivatives. Trans. R. Soc. Trop. Med. Hyg., 2006, 100 (Suppl 1), S4-8.
116. Sundar, S.; Jha, T.K.; Thakur, C.P.; Engel, J.; Sindermann, H.; Fischer, C.; Junge, K.; Bryceson, A.; Berman, J. Oral miltefosine for Indian visceral leishmaniasis. N. Engl. J. Med., 2002, 347, 1739-1746.
117. Soto, J.; Arana, B.A.; Toledo, J.; Rizzo, N.; Vega, J.C.; Diaz, A.; Luz, M.; Gutierrez, P.; Arboleda, M.; Berman, J.D.; Junge, K.; Engel, J.; Sindermann, H. Miltefosine for new world cutaneous leishmaniasis. Clin. Infect. Dis., 2004, 38, 1266-1272.
118. Yardley, V.; Croft, S.L.; De Doncker, S.; Dujardin, J.C.; Koirala, S.; Rijal, S.; Miranda, C.; Llanos-Cuentas, A.; Chappuis, F. The sensitivity of clinical isolates of Leishmania from Peru and Nepal to miltefosine. Am. J. Trop. Med. Hyg., 2005, 73, 272-275.
119. Perez-Victoria, F.J.; Castanys, S.; Gamarro, F. Leishmania donovani resistance to miltefosine involves a defective inward translocation of the drug. Antimicrob. Agents Chemother., 2003, 47, 2397-2403.
120. Croft, S.L.; Sundar, S.; Fairlamb, A.H. Drug resistance in leishmaniasis. Clin. Microbiol. Rev., 2006, 19, 111-126.
121. Eibl, H.; Unger, C. Hexadecylphosphocholine: A new and selective antitumor drug. Cancer Treat. Rev., 1990, 17, 233-242.
122. Jha, T.K.; Sundar, S.; Thakur, C.P.; Bachmann, P.; Karbwang, J.; Fischer, C.; Voss, A.; Berman, J. Miltefosine, an oral agent, for the treatment of Indian visceral leishmaniasis. N. Engl. J. Med., 1999, 341, 1795-1800.
123. Bhattacharya, S.K.; Sinha, P.K.; Sundar, S.; Thakur, C.P.; Jha, T.K.; Pandey, K.; Das, V.R.; Kumar, N.; Lal, C.; Verma, N.; Singh, V.P.; Ranjan, A.; Verma, R.B.; Anders, G.; Sindermann, H.; Ganguly, N.K. Phase 4 trial of miltefosine for the treatment of Indian visceral leishmaniasis. J. Infect. Dis., 2007, 196, 591-598.
124. Sindermann, H.; Engel, J. Development of miltefosine as an oral treatment for leishmaniasis. Trans. R. Soc. Trop. Med. Hyg., 2006, 100 (Suppl 1), S17-20.
125. Mishra, J.; Saxena, A.; Singh, S. Chemotherapy of leishmaniasis: Past, present and future. Curr. Med. Chem., 2007, 14, 1153-1169.
126. Thakur, C.P.; Kanyok, T.P.; Pandey, A.K.; Sinha, G.P.; Messick, C.; Olliaro, P. Treatment of visceral leishmaniasis with injectable paromomycin (aminosidine). An open-label randomized phase-II clinical study. Trans. R. Soc. Trop. Med. Hyg., 2000, 94, 432-433.
127. Armijos, R.X.; Weigel, M.M.; Calvopina, M.; Mancheno, M.; Rodriguez, R. Comparison of the effectiveness of two topical paromomycin treatments versus meglumine antimoniate for New World cutaneous leishmaniasis. Acta Trop., 2004, 91, 153-160.
128. Bryceson, A.D.; Murphy, A.; Moody, A.H. Treatment of 'Old World' cutaneous leishmaniasis with aminosidine ointment: Results of an open study in London. Trans. R. Soc. Trop. Med. Hyg., 1994, 88, 226-228.
129. Sundar, S.; Jha, T.K.; Thakur, C.P.; Sinha, P.K.; Bhattacharya, S.K. Injectable paromomycin for Visceral leishmaniasis in India. N. Engl. J. Med., 2007, 356, 2571-2581.
130. Maarouf, M.; de Kouchkovsky, Y.; Brown, S.; Petit, P.X.; Robert-Gero, M. In vivo interference of paromomycin with mitochondrial activity of Leishmania. Exp. Cell. Res., 1997, 232, 339-348
131. Maarouf, M.; Lawrence, F.; Croft, S.L.; Robert-Gero, M. Ribosomes of Leishmania are a target for the aminoglycosides. Parasitol. Res., 1995, 81, 421-425.
132. Sherwood, J. A.; Gachihi, G. S.; Muigai, R. K.; Skillman, D. R.; Mugo, M.; Rashid, J. R.; Wasunna, K. M.; Were, J. B.; Kasili, S. K.; Mbugua, J. M.; Kirigi, G.; Schaefer, K.U.; Oster, C.N.; Fleckenstein, L.L.; Berman, J.D.; Brewer, T.G.; Roberts, C.R.; Johnson, A.J.; Schuster, B.G. Phase 2 efficacy trial of an oral 8-aminoquinoline (WR6026) for treatment of visceral leishmaniasis. Clin. Infect. Dis., 1994, 19, 1034-1039.
133. 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, 1005-1011.
134. Wasunna, M.K.; Rashid, J.R.; Mbui, J.; Kirigi, G.; Kinoti, D.; Lodenyo, H.; Felton, J.M.; Sabin, A.J.; Albert, M.J.; Horton, J. A phase II dose-increasing study of sitamaquine for the treatment of visceral leishmaniasis in Kenya. Am. J. Trop. Med. Hyg., 2005, 73, 871-876.
135. Tekwani, B.L.; Walker, L.A. 8-Aminoquinolines: Future role as antiprotozoal drugs. Curr. Opin. Infect. Dis., 2006, 19, 623-631.
136. Alrajhi, A.A.; Ibrahim, E.A.; De Vol, E.B.; Khairat, M.; Faris, R.M.; Maguire, J.H. Fluconazole for the treatment of cutaneous leishmaniasis caused by Leishmania major. N. Engl. J. Med., 2002, 346, 891-895.
137. Calvopina, M.; Guevara, A.G.; Armijos, R.X.; Hashiguchi, Y.; Davidson, R.N.; Cooper, P.J. Itraconazole in the treatment of new world mucocutaneous leishmaniasis. Int. J. Dermatol., 2004, 43, 659-663.
138. Momeni, A.Z.; Jalayer, T.; Emamjomeh, M.; Bashardost, N.; Ghassemi, R.L.; Meghdadi, M.; Javadi, A.; Aminjavaheri, M. Treatment of cutaneous leishmaniasis with itraconazole. Randomized double-blind study. Arch. Dermatol., 1996, 132, 784-786.
139. Nassiri-Kashani, M.; Firooz, A.; Khamesipour, A.; Mojtahed, F.; Nilforoushzadeh, M.; Hejazi, H.; Bouzari, N.; Dowlati, Y. A randomized, double-blind, placebo-controlled clinical trial of itraconazole in the treatment of cutaneous leishmaniasis. J. Eur. Acad. Dermatol. Venereol., 2005, 19, 80-83.
140. Al-Abdely, H.M.; Graybill, J.R.; Loebenberg, D.; Melby, P.C. Efficacy of the triazole SCH 56592 against Leishmania amazonensis and Leishmania donovani in experimental murine cutaneous and visceral leishmaniases. Antimicrob. Agents Chemother., 1999, 43, 2910-2914
141. Salmanpour, R.; Handjani, F.; Nouhpisheh, M.K. Comparative study of the efficacy of oral ketoconazole with intra-lesional meglumine antimoniate (Glucantime) for the treatment of cutaneous leishmaniasis. J. Dermatolog. Treat., 2001, 12, 159-162.
142. Momeni, A.Z.; Aminjavaheri, M.; Omidghaemi, M.R. Treatment of cutaneous leishmaniasis with ketoconazole cream. J. Dermatolog. Treat., 2003, 14, 26-29.
143. Suzuki, H.; Wang, B.; Shivji, G.M.; Toto, P.; Amerio, P.; Tomai, M.A.; Miller, R.L.; Sauder, D.N. Imiquimod, a topical immune response modifier, induces migration of Langerhans cells. J. Invest. Dermatol., 2000, 114, 135-141.
144. Skinner, R.B. Jr. Imiquimod. Dermatol. Clin., 2003, 21, 291-300.
145. Buates, S.; Matlashewski, G. Treatment of experimental leishmaniasis with the immunomodulators imiquimod and S-28463: Efficacy and mode of action. J. Infect. Dis., 1999, 179, 1485-1494.
146. Arevalo, I.; Ward, B.; Miller, R.; Meng, T.C.; Najar, E.; Alvarez, E.; Matlashewski, G.; Llanos-Cuentas, A. Successful treatment of drug-resistant cutaneous leishmaniasis in humans by use of imiquimod, an immunomodulator. Clin. Infect. Dis., 2001, 33, 1847-1851.
147. Firooz, A.; Khamesipour, A.; Ghoorchi, M.H.; Nassiri-Kashani, M.; Eskandari, S.E.; Khatami, A.; Hooshmand, B.; Gorouhi, F.; Rashighi-Firoozabadi, M.; Dowlati, Y. Imiquimod in combination with meglumine antimoniate for cutaneous leishmaniasis: A randomized assessor-blind controlled trial. Arch. Dermatol., 2006, 142, 1575-1579.
148. El-On, J.; Bazarsky, E.; Sneir, R. Leishmania major: in vitro and in vivo anti-leishmanial activity of paromomycin ointment (Leshcutan) combined with the immunomodulator Imiquimod. Exp. Parasitol., 2007, 116, 156-162.
149. Seeberger, J.; Daoud, S.; Pammer, J. Transient effect of topical treatment of cutaneous leishmaniasis with imiquimod. Int. J. Dermatol., 2003, 42, 576-579.
150. Fournet, A.; Munoz, V. Natural products as trypanocidal, antileishmanial and antimalarial drugs. Curr. Top. Med. Chem., 2002, 2, 1215-1237.
151. Muhammad, I.; Dunbar, D.C.; Khan, S.I.; Tekwani, B.L.; Bedir, E.; Takamatsu, S.; Ferreira, D.; Walker, L.A. Antiparasitic alkaloids from Psychotria klugii. J. Nat. Prod., 2003, 66, 962-967.
152. Sairafianpour, M.; Christensen, J.; Staerk, D.; Budnik, B.A.; Kharazmi, A.; Bagherzadeh, K.; Jaroszewski, J.W. Leishmanicidal, antiplasmodial, and cytotoxic activity of novel diterpenoid 1,2-quinones from Perovskia abrotanoides: New source of tanshinones. J. Nat. Prod., 2001, 64, 1398-1403.
153. Fuchino, H.; Koide, T.; Takahashi, M.; Sekita, S.; Satake, M. New sesquiterpene lactones from Elephantopus mollis and their leishmanicidal activities. Planta Med., 2001, 67, 647-653.
154. Barata, L.E.; Santos, L.S.; Ferri, P.H.; Phillipson, J.D.; Paine, A.; Croft, S.L. Anti-leishmanial activity of neolignans from Virola species and synthetic analogues. Phytochemistry, 2000, 55, 589-595.
155. Kayser, O.; Kiderlen, A.F.; Laatsch, H.; Croft, S.L. In vitro leishmanicidal activity of monomeric and dimeric naphthoquinones. Acta Trop., 2000, 77, 307-314.
156. Rao, K.V.; Kasanah, N.; Wahyuono, S.; Tekwani, B.L.; Schinazi, R.F.; Hamann, M.T. Three new manzamine alkaloids from a common Indonesian sponge and their activity against infectious and tropical parasitic diseases. J. Nat. Prod., 2004, 67, 1314-1318.
157. Torres-Santos, E.C.; Lopes, D.; Oliveira, R.R.; Carauta, J.P.; Falcao, C.A.; Kaplan, M.A.; Rossi-Bergmann, B. Antileishmanial activity of isolated triterpenoids from Pourouma guianensis. Phytomedicine, 2004, 11, 114-120.
158. Okpekon, T.; Yolou, S.; Gleye, C.; Roblot, F.; Loiseau, P.; Bories, C.; Grellier, P.; Frappier, F.; Laurens, A.; Hocquemiller, R. Antiparasitic activities of medicinal plants used in Ivory Coast. J. Ethnopharmacol., 2004, 90, 91-97.
159. Takahashi, M.; Fuchino, H.; Sekita, S.; Satake, M. In vitro leishmanicidal activity of some scarce natural products. Phytother. Res., 2004, 18, 573-578.
160. Cabrera-Serra, M.G.; Lorenzo-Morales, J.; Romero, M.; Valladares, B.; Pinero, J.E. In vitro activity of perifosine: A novel alkylphospholipid against the promastigote stage of Leishmania species. Parasitol. Res., 2007, 100, 1155-1157.
161. Desrivot, J.; Herrenknecht, C.; Ponchel, G.; Garbi, N.; Prina, E.; Fournet, A.; Bories, C.; Figadere, B.; Hocquemiller, R.; Loiseau, P.M. Antileishmanial 2-substituted quinolines: in vitro behaviour towards biological components. Biomed. Pharmacother., 2007, 61, 441-450.
162. Maes, L.; Germonprez, N.; Quirijnen, L.; Van Puyvelde, L.; Cos, P.; Vanden Berghe, D. Comparative activities of the triterpene saponin maesabalide III and liposomal amphotericin B (AmBisome) against Leishmania donovani in hamsters. Antimicrob. Agents Chemother., 2004, 48, 2056-2060.
163. Flores, N.; Cabrera, G.; Jimenez, I.A.; Pinero, J.; Gimenez, A.; Bourdy, G.; Cortes-Selva, F.; Bazzocchi, I.L. Leishmanicidal constituents from the leaves of Piper rusbyi. Planta Med., 2007, 73, 206-211.
164. Lakshmi, V.; Pandey, K.; Kapil, A.; Singh, N.; Samant, M.; Dube, A. In vitro and in vivo leishmanicidal activity of Dysoxylum binectariferum and its fractions against Leishmania donovani. Phytomedicine, 2007, 14, 36-42.
165. Tasdemir, D.; Kaiser, M.; Brun, R.; Yardley, V.; Schmidt, T.J.; Tosun, F.; Ruedi, P. Antitrypanosomal and antileishmanial activities of flavonoids and their analogues: in vitro, in vivo, structure-activity relationship, and quantitative structure-activity relationship studies. Antimicrob. Agents Chemother., 2006, 50, 1352-1364.
166. Siemann, E.H.; Creasy, L.L. Concentration of the phytoalexin resveratrol in wine. Am J. Enol. Vitic., 1992, 43, 49-52.
167. Baur, J.A.; Sinclair, D.A. Therapeutic potential of resveratrol: The in vivo evidence. Nat. Rev. Drug Discov., 2006, 5, 493-506.
168. Leiro, J.; Arranz, J.A.; Parama, A.; Alvarez, M.F.; Sanmartin, M.L. In vitro effects of the polyphenols resveratrol, mangiferin and (-)- epigallocatechin-3-gallate on the scuticociliate fish pathogen Philasterides dicentrarchi. Dis. Aquat. Organ., 2004, 59, 171-174.
169. Son, I.H.; Chung, I.M.; Lee, S.J.; Moon, H.I. Antiplasmodial activity of novel stilbene derivatives isolated from Parthenocissus tricuspidata from South Korea. Parasitol. Res., 2007, 101, 237-241.
170. Juan, M.E.; Vinardell, M.P.; Planas, J.M. The daily oral administration of high doses of trans-resveratrol to rats for 28 days is not harmful. J. Nutr., 2002, 132, 257-260.
171. Kedzierski, L.; Curtis, J.M.; Kaminska, M.; Jodynis-Liebert, J.; Murias, M. In vitro antileishmanial activity of resveratrol and its hydroxylated analogues against Leishmania major promastigotes and amastigotes. Parasitol. Res., 2007, 102, 91-97
172. Leiro, J.; Cano, E.; Ubeira, F.M.; Orallo, F.; Sanmartin, M.L. In vitro effects of resveratrol on the viability and infectivity of the microsporidian Encephalitozoon cuniculi. Antimicrob. Agents Chemother., 2004, 48, 2497-2501.
173. Dobrydneva, Y.; Williams, R.L.; Blackmore, P.F. trans-Resveratrol inhibits calcium influx in thrombin-stimulated human platelets. Br. J. Pharmacol., 1999, 128, 149-157.
174. Feng, Y.H.; Zhou, W.L.; Wu, Q.L.; Li, X.Y.; Zhao, W.M.; Zou, J.P. Low dose of resveratrol enhanced immune response of mice. Acta Pharmacol. Sin., 2002, 23, 893-897.
175. Zasloff, M. Antimicrobial peptides of multicellular organisms. Nature, 2002, 415, 389-395.
176. Vizioli, J.; Salzet, M. Antimicrobial peptides versus parasitic infections? Trends Parasitol., 2002, 18, 475-476
177. Vouldoukis, I.; Shai, Y.; Nicolas, P.; Mor, A. Broad spectrum antibiotic activity of the skin-PYY. FEBS Lett., 1996, 380, 237-240.
178. Feder, R.; Dagan, A.; Mor, A. Structure-activity relationship study of antimicrobial dermaseptin S4 showing the consequences of peptide oligomerization on selective cytotoxicity. J. Biol. Chem., 2000, 275, 4230-4238.
179. Brand, G.D.; Leite, J.R.; de Sa Mandel, S.M.; Mesquita, D.A.; Silva, L.P.; Prates, M.V.; Barbosa, E.A.; Vinecky, F.; Martins, G.R.; Galasso, J.H.; Kuckelhaus, S.A.; Sampaio, R.N.; Furtado, J.R. Jr.; Andrade, A.C.; Bloch, C. Jr. Novel dermaseptins from Phyllomedusa hypochondrialis (Amphibia). Biochem. Biophys. Res. Commun., 2006, 347, 739-746.
180. Akuffo, H.; Hultmark, D.; Engstom, A.; Frohlich, D.; Kimbrell, D. Drosophila antibacterial protein, cecropin A, differentially affects non-bacterial organisms such as Leishmania in a manner different from other amphipathic peptides. Int. J. Mol. Med., 1998, 1, 77-82.
181. Diaz-Achirica, P.; Ubach, J.; Guinea, A.; Andreu, D.; Rivas, L. The plasma membrane of Leishmania donovani promastigotes is the main target for CA(1-8)M(1-18), a synthetic cecropin A-melittin hybrid peptide. Biochem. J., 1998, 330 (Pt 1), 453-460.
182. Silva, P.I. Jr.; Daffre, S.; Bulet, P. Isolation and characterization of gomesin, an 18-residue cysteine-rich defense peptide from the spider Acanthoscurria gomesiana hemocytes with sequence similarities to horseshoe crab antimicrobial peptides of the tachyplesin family. J. Biol. Chem., 2000, 275, 33464-33470.
183. Mangoni, M.L.; Papo, N.; Saugar, J.M.; Barra, D.; Shai, Y.; Simmaco, M.; Rivas, L. Effect of natural L- to D-amino acid conversion on the organization, membrane binding, and biological function of the antimicrobial peptides bombinins H. Biochemistry, 2006, 45, 4266-4276.
184. Bera, A.; Singh, S.; Nagaraj, R.; Vaidya, T. Induction of autophagic cell death in Leishmania donovani by antimicrobial peptides. Mol. Biochem. Parasitol., 2003, 127, 23-35.
185. Kulkarni, M.M.; McMaster, W.R.; Kamysz, E.; Kamysz, W.; Engman, D.M.; McGwire, B.S. The major surface-metalloprotease of the parasitic protozoan, Leishmania, protects against antimicrobial peptide-induced apoptotic killing. Mol. Microbiol., 2006, 62, 1484-1497.
186. Guerrero, E.; Saugar, J.M.; Matsuzaki, K.; Rivas, L. Role of positional hydrophobicity in the leishmanicidal activity of magainin 2. Antimicrob. Agents Chemother., 2004, 48, 2980-2986
187. Mangoni, M.L. Temporins, anti-infective peptides with expanding properties. Cell. Mol. Life Sci., 2006, 63, 1060-1069.
188. Roch, P.; Beschin, A.; Bernard, E. Antiprotozoan and Antiviral Activities of Non-cytotoxic Truncated and Variant Analogues of Mussel Defensin. Evid. Based Complement. Alternat. Med., 2004, 1, 167-174.
189. Lofgren, S.E.; Miletti, L.C.; Steindel, M.; Bachere, E.; Barracco, M.A. Trypanocidal and leishmanicidal activities of different antimicrobial peptides (AMPs) isolated from aquatic animals. Exp. Parasitol., 2008, 118, 197-202.
190. Alberola, J.; Rodriguez, A.; Francino, O.; Roura, X.; Rivas, L.; Andreu, D. Safety and efficacy of antimicrobial peptides against naturally acquired leishmaniasis. Antimicrob. Agents Chemother., 2004, 48, 641-643.
191. Yang, D.; Biragyn, A.; Kwak, L.W.; Oppenheim, J.J. Mammalian defensins in immunity: More than just microbicidal. Trends Immunol., 2002, 23, 291-296.
192. Salzet, M. Antimicrobial peptides are signaling molecules. Trends Immunol., 2002, 23, 283-284.
193. Hancock, R.E.; Sahl, H.G. Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat. Biotechnol., 2006, 24, 1551-1557.
194. Drews, J. Drug discovery: A historical perspective. Science, 2000, 287, 1960-1964.
195. D'Silva, C.; Daunes, S. The therapeutic potential of inhibitors of the trypanothione cycle. Expert Opin. Investig. Drugs, 2002, 11, 217-231.
196. Verlinde, C.L.; Hannaert, V.; Blonski, C.; Willson, M.; Perie, J.J.; Fothergill-Gilmore, L.A.; Opperdoes, F.R.; Gelb, M.H.; Hol, W.G.; Michels, P.A. Glycolysis as a target for the design of new antitrypanosome drugs. Drug Resist. Updat., 2001, 4, 50-65.
197. Urbina, J.A.; Concepcion, J.L.; Rangel, S.; Visbal, G.; Lira, R. Squalene synthase as a chemotherapeutic target in Trypanosoma cruzi and Leishmania mexicana. Mol. Biochem. Parasitol., 2002, 125, 35-45.
198. Moyersoen, J.; Choe, J.; Fan, E.; Hol, W.G.; Michels, P.A. Biogenesis of peroxisomes and glycosomes: Trypanosomatid glycosome assembly is a promising new drug target. FEMS Microbiol. Rev., 2004, 28, 603-643.
199. Uboldi, A.D.; Lueder, F.B.; Walsh, P.; Spurck, T.; McFadden, G.I.; Curtis, J.; Likic, V.A.; Perugini, M.A.; Barson, M.; Lithgow, T.; Handman, E. A mitochondrial protein affects cell morphology, mitochondrial segregation and virulence in Leishmania. Int. J. Parasitol., 2006, 36, 1499-1514.
200. Mottram, J.C.; Coombs, G.H.; Alexander, J. Cysteine peptidases as virulence factors of Leishmania. Curr. Opin. Microbiol., 2004, 7, 375-381.
201. Das, B.B.; Ganguly, A.; Majumder, H.K. DNA topoisomerases of Leishmania: the potential targets for anti-leishmanial therapy. Adv. Exp. Med. Biol., 2008, 625, 103-115.
202. Davis, A.J.; Perugini, M.A.; Smith, B.J.; Stewart, J.D.; Ilg, T.; Hodder, A.N.; Handman, E. Properties of GDP-mannose pyrophosphorylase, a critical enzyme and drug target in Leishmania mexicana. J. Biol. Chem., 2004, 279, 12462-12468.
203. Kedzierski, L.; Malby, R.L.; Smith, B.J.; Perugini, M.A.; Hodder, A.N.; Ilg, T.; Colman, P.M.; Handman, E. Structure of Leishmania mexicana phosphomannomutase highlights similarities with human isoforms. J. Mol. Biol., 2006, 363, 215-227.
204. Hunter, W.N. A structure-based approach to drug discovery; crystallography and implications for the development of antiparasite drugs. Parasitology, 1997, 114 (Suppl), S17-29.
205. Austin, S.E.; Khan, M.O.; Douglas, K.T. Rational drug design using trypanothione reductase as a target for anti-trypanosomal and anti-leishmanial drug leads. Drug Des. Discov., 1999, 16, 5-23.
206. Dardonville, C.; Rinaldi, E.; Hanau, S.; Barrett, M.P.; Brun, R.; Gilbert, I.H. Synthesis and biological evaluation of substrate-based inhibitors of 6-phosphogluconate dehydrogenase as potential drugs against African trypanosomiasis. Bioorg. Med. Chem., 2003, 11, 3205-3214.
207. Bressi, J.C.; Verlinde, C.L.; Aronov, A.M.; Shaw, M.L.; Shin, S.S.; Nguyen, L.N.; Suresh, S.; Buckner, F.S.; Van Voorhis, W.C.; Kuntz, I.D.; Hol, W.G.; Gelb, M.H. Adenosine analogues as selective inhibitors of glyceraldehyde-3-phosphate dehydrogenase of Trypanosomatidae via structure-based drug design. J. Med. Chem., 2001, 44, 2080-2093.
208. Walters, W.P.; Namchuk, M. Designing screens: How to make your hits a hit. Nat. Rev. Drug Discov., 2003, 2, 259-266.
209. 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, 1971-1982.
210. 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, 441-452.
211. 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, 312-324.
212. Labadie, G.R.; Choi, S.R.; Avery, M.A. Diamine derivatives with antiparasitic activities. Bioorg. Med. Chem. Lett., 2004, 14, 615-619.
213. Hinshaw, J.C.; Suh, D.Y.; Garnier, P.; Buckner, F.S.; Eastman, R.T.; Matsuda, S.P.; Joubert, B.M.; Coppens, I.; Joiner, K.A.; Merali, S.; Nash, T.E.; Prestwich, G.D. Oxidosqualene cyclase inhibitors as antimicrobial agents. J. Med. Chem., 2003, 46, 4240-4243.
214. Grant, K.M.; Dunion, M.H.; Yardley, V.; Skaltsounis, A.L.; Marko, D.; Eisenbrand, G.; Croft, S.L.; Meijer, L.; Mottram, J.C. Inhibitors of Leishmania mexicana CRK3 cyclin-dependent kinase: Chemical library screen and antileishmanial activity. Antimicrob. Agents Chemother., 2004, 48, 3033-3042.