Leishmaniasis: Drug resistance and natural products (review)

International Journal of Molecular Medicine

Volumn 22, Issue 3, 2008, Pages 277-286

  Polonio, Tilman ^a   Efferth, Thomas ^b  

^a UNIVERSITY OF HEIDELBERG   (Germany)

^b GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

Author keywords

Anti viral agents; Chemotherapy; Drug resistance; Leishmaniasis; Natural products; Pharmacognosy

Indexed keywords

ALLOPURINOL; AMAROGENTIN; AMPHOTERICIN B; AMPHOTERICIN B DEOXYCHOLATE; AMPHOTERICIN B LIPID COMPLEX; ANTIMONY; CHALCONE DERIVATIVE; COUMARIN; DIPROPHYLLINE; FLAVONOID; IRIDOID; LICOCHALCONE A; LIGNAN; LUTEOLIN; MEGLUMINE ANTIMONATE; MILTEFOSINE; NAPHTHOQUINONE; PAROMOMYCIN; PENTAMIDINE; PENTAMIDINE ISETHIONATE; PLUMBAGIN; PYRROLE DERIVATIVE; QUERCETIN; QUINOLINE DERIVED ANTIINFECTIVE AGENT; SAPONIN; SITAMAQUINE; STIBOGLUCONATE SODIUM; TAXOID; TERPENE; UNINDEXED DRUG; BIOLOGICAL PRODUCT;

ANTIPROTOZOAL ACTIVITY; CLINICAL FEATURE; CLINICAL TRIAL; DISEASE TRANSMISSION; DRUG DESIGN; DRUG FORMULATION; DRUG ISOLATION; DRUG PROTEIN BINDING; DRUG SCREENING; DRUG STRUCTURE; DRUG TRANSPORT; ECG ABNORMALITY; ENDEMIC DISEASE; HUMAN; LEISHMANIA; LEISHMANIASIS; NEPHROTOXICITY; NONHUMAN; PANCREATITIS; PREVALENCE; PRIORITY JOURNAL; REVIEW; SIDE EFFECT; SYMPTOMATOLOGY; ANIMAL; CHEMISTRY; DRUG EFFECT; DRUG RESISTANCE;

ANIMALS; BIOLOGICAL PRODUCTS; DRUG EVALUATION, PRECLINICAL; DRUG RESISTANCE; HUMANS; LEISHMANIASIS;

EID: 53049090855     PISSN: 11073756     EISSN: None     Source Type: Journal    
DOI: 10.3892/ijmm_00000020     Document Type: Review

References (92)

1. Kedzierski L, Zhu Y and Handman E: Leishmania vaccines: progress and problems. Parasitology 133: S87-S 112, 2006.
2. Sukumaran B and Madhubala R: Leishmaniasis: current status of vaccine development. Curr Mol Med 4: 667-679, 2004.
3. Ghosh M and Bandyopadhyay S: Present status of antileishmanial vaccines. Mol Cell Biochem 253: 199-205, 2003.
4. Desjeux P: Worldwide increasing risk factors for leishmaniasis. Med Microbiol Immunol 190: 77-79, 2001.
5. Desjeux P: Leishmaniasis: current situation and new perspectives. Comp Immunol Microbiol Infect Dis 27: 305-318, 2004.
6. Murray HW, Berman JD, Davies CR and Saravia NG: Advances in leishmaniasis. Lancet 366: 1561-1577, 2005.
7. Rosenthal E and Marty P: Recent understanding in the treatment of visceral leishmaniasis. J Postgrad Med 49: 61-68, 2003.
8. Chappuis F, Sundar S, Hailu A, et al: Visceral leishmaniasis: what are the needs for diagnosis, treatment and control? Nat Rev Microbiol 5: 873-882, 2007.
9. Hepburn NC: Cutaneous leishmaniasis: an overview. J Postgrad Med 49: 50-54, 2003.
10. Amato VS, Tuon FF, Bacha HA, Neto VA and Nicoderno AC: Mucosal leishmaniasis. Current scenario and prospects for treatment. Acta Trop 105: 1-9, 2008.
11. Sacks D and Noben-Trauth N: The immunology of susceptibility and resistance to Leishmania major in mice. Nat Rev Immunol 2: 845-858, 2002.
12. Von Stebut E and Udey MC: Requirements for Th1-dependent immunity against infection with Leishmania major. Microbes Infect 6: 1102-1109, 2004.
13. Sundar S, More DK, Singh MK, et al: Failure of pentavalent antimony in visceral leishmaniasis in India: report from the center of the Indian epidemic. Clin Infect Dis 31: 1104-1107, 2000.
14. Gourbal B, Sonuc N, Bhattacharjee H, et al: Drug uptake and modulation of drug resistance in Leishmania by an aquaglyceroporin. J Biol Chem 279: 31010-31017, 2004.
15. Ashutosh, Sundar S and Goyal N: Molecular mechanisms of antimony resistance in Leishmania. J Med Microbiol 56: 143-153, 2007.
16. Zhou Y, Messier N, Ouellette M, Rosen BP and Mukhopadhyay R: Leishmania major LmACR2 is a pentavalent antimony reductase that confers sensitivity to the drug pentostam. J Biol Chem 279: 37445-37451, 2004.
17. Denton H, McGregor JC and Coombs GH: Reduction of anti-leishmanial pentavalent antimonial drugs by a parasite-specific thiol-dependent reductase, TDR1. Biochem J 381: 405-412, 2004.
18. Yan S, Li F, Ding K and Sun H: Reduction of pentavalent antimony by trypanothione and formation of a binary and ternary complex of antimony(III) and trypanothione. J Biol Inorg Chem 8: 689-697, 2003.
19. Ferreira Cdos S, Martins PS, Demicheli C, Brochu C, Ouellette M and Frezard F: Thiol-induced reduction of antimony(V) into antimony(III): a comparative study with trypanothione, cysteinyl-glycine, cysteine and glutathione. Biometals 16: 441-446, 2003.
20. Wyllie S, Cunningham ML and Fairlamb AH: Dual action of antimonial drugs on thiol redox metabolism in the human pathogen Leishmania donovani. J Biol Chem 279: 39925-39932, 2004.
21. Mukherjee A, Padmanabhan PK, Singh S, et al: Role of ABC transporter MRPA, gamma-glutamylcysteine synthetase and ornithine decarboxylase in natural antimony-resistant isolates of Leishmania donovani. J Antimicrob Chemother 59: 204-211, 2007.
22. Decuypere S, Rijal S, Yardley V, et al: Gene expression analysis of the mechanism of natural Sb(V) resistance in Leishmania donovani isolates from Nepal. Antimicrob Agents Chemother 49: 4616-4621, 2005.
23. El Fadili K, Messier N, Leprohon P, et al: Role of the ABC transporter MRPA (PGPA) in antimony resistance in Leishmania infantum axenic and intracellular amastigotes. Antimicrob Agents Chemother 49: 1998-1993, 2005.
24. Mookerjee Basu J, Mookerjee A, Banerjee R, et al: Inhibition of ABC transporters abolishes antimony resistance in Leishmania infection. Antimicrob Agents Chemother 52: 1080-1093, 2008.
25. Adler-Moore J and Proffitt RT: AmBisome: liposomal formulation, structure, mechanism of action and pre-clinical experience. J Antimicrob Chemother 49 (Suppl 1): 21-30, 2002.
26. Saha AK, Mukherjee T and Bhaduri A: Mechanism of action of amphotericin B on Leishmania donovani promastigotes. Mol Biochem Parasitol 19: 195-200, 1986.
27. Ramos H, Valdivieso E, Gamargo M, Dagger F and Cohen BE: Amphotericin B kills unicellular leishmanias by forming aqueous pores permeable to small cations and anions. J Membr Biol 152: 65-75, 1996.
28. Mbongo N, Loiseau PM, Billion MA and Robert-Gero M: Mechanism of amphotericin B resistance in Leishmania donovani promastigotes. Antimicrob Agents Chemother 42: 352-357, 1998.
29. Al-Mohammed HI, Chance ML and Bates PA: Production and characterization of stable amphotericin-resistant amastigotes and promastigotes of Leishmania mexicana. Antimicrob Agents Chemother 49: 3274-3280, 2005.
30. Pourshafie M, Morand S, Virion A, Rakotomanga M, Dupuy C and Loiseau PM: Cloning of S-adenosyl-L-methionine:C-24- Delta-sterol-methyltransferase (ERG6) from Leishmania donovani and characterization of mRNAs in wild-type and amphotericin B-resistant promastigotes. Antimicrob Agents Chemother 48: 2409-2414, 2004.
31. Bhattacharya SK, Sinha PK, Sundar S, et al: Phase 4 trial of miltefosine for the treatment of Indian visceral leishmaniasis. J Infect Dis 196: 591-598, 2007.
32. Croft SL and Coombs GH: Leishmaniasis - current chemotherapy and recent advances in the search for novel drugs. Trends Parasitol 19: 502-508, 2003.
33. Perez-Victoria FJ, Sanchez-Canete MP, Seifert K, et al: Mechanisms of experimental resistance of Leishmania to miltefosine: implications for clinical use. Drug Resist Updat 9: 26-39, 2006.
34. Pérez-Victoria FJ, Gamarro F, Ouellette M and Castanys S: Functional cloning of the miltefosine transporter. J Biol Chem 278: 49965-49971, 2003.
35. Perez-Victoria FJ, Sanchez-Canete MP, Castanys S and Gamarro F: Phospholipid translocation and miltefosine potency require both L. donovani miltefosine transporter and the new protein LdRos3 in Leishmania parasites. J Biol Chem 281: 23766-23775, 2006.
36. Verma NK and Dey CS: Possible mechanism of miltefosine-mediated death of Leishmania donovani. Antimicrob Agents Chemother 48: 3010-3015, 2004.
37. Lux H, Heise N, Klenner T, Hart D and Opperdoes FR: Etherlipid (alkyl-phospholipid) metabolism and the mechanism of action of ether-lipid analogues in Leishmania. Mol Biochem Parasitol 111: 1-14, 2000.
38. Perez-Victoria JM, Perez-Victoria FJ, Parodi-Talice A, et al: Alkyl-lysophospholipid resistance in multidrug-resistant Leishmania tropica and chemosensitization by a novel P-glycoprotein-like transporter modulator. Antimicrob Agents Chemother 45: 2468-2474, 2001.
39. Seifert K, Perez-Victoria FJ, Stettler M, et al: Inactivation of the miltefosine transporter, LdMT, causes miltefosine resistance that is conferred to the amastigote stage of Leishmania donovani and persists in vivo. Int J Antimicrob Agents 30: 229-235, 2007.
40. Castanys-Munoz; E, Alder-Baerens N, Pomorski T, Gamarro F and Castanys S: A novel ATP-binding cassette transporter from Leishmania is involved in transport of phosphatidylcholine analogues and resistance to alkyl-phospholipids. Mol Microbiol 64: 1141-1153, 2007.
41. Sundar S: Drug resistance in Indian visceral leishmaniasis. Trop Med Int Health 6: 849-854, 2001.
42. Singh G and Dey CS: Induction of apoptosis-like cell death by pentamidine and doxorubicin through differential inhibition of topoisomerase II in arsenite-resistant L. donovani. Acta Trop, 103: 172-185, 2007.
43. Bray PG, Barrett MP, Ward SA and de Koning HP: Pentamidine uptake and resistance in pathogenic protozoa: past, present and future. Trends Parasitol 19: 232-239, 2003.
44. Mehta A and Shaba C: Apoptotic death in Leishmania donovani promastigotes in response to respiratory chain inhibition: complex II inhibition results in increased pentamidine cytotoxicity. J Biol Chem 279: 11798-11813, 2004.
45. Coelho AC, Messier N, Ouellette M and Cotrim PC: Role of the ABC transporter PRP1 (ABCC7) in pentamidine resistance in Leishmania amastigotes. Antimicrob Agents Chemother 51: 3030-3032, 2007.
46. Maarouf M, Lawrence F, Croft SL and Robert-Gero M: Ribosomes of Leishmania are a target for the aminoglycosides. Parasitol Res 81: 421-425, 1995.
47. Maarouf M, Lawrence F, Brown S and Robert-Gero M: Biochemical alterations in paromomycin-treated Leishmania donovani promastigotes. Parasitol Res 83: 198-202, 1997.
48. Maarouf M, de Kouchkovsky Y, Brown S, Petit PX and Robert-Gero M: In vivo interference of paromomycin with mitochondrial activity of Leishmania. Exp Cell Res 232: 339-348, 1997.
49. Maarouf M, Adeline MT, Solignac M, Vautrin D and Robert-Gero M: Development and characterization of paromomycin-resistant Leishmania donovani promastigotes. Parasite 5: 167-173, 1998.
50. Esfandiarpour I and Alavi A: Evaluating the efficacy of allopurinol and meglumine antimoniate (Glucantime) in the treatment of cutaneous leishmaniasis. Int J Dermatol 41: 521-524, 2002.
51. Das VN, Ranjan A, Sinha AN, et al: A randomized clinical trial of low dosage combination of pentamidine and allopurinol in the treatment of antimony unresponsive cases of visceral leishmaniasis. J Assoc Physicians India 49: 609-613, 2001.
52. Yeates C: Sitamaquine (GlaxoSmithKline/Walter Reed Army Institute). Curr Opin Investig Drugs 3: 1446-1452, 2002.
53. Wasunna MK, Rashid JR, Mbui J, et al: A phase II dose-increasing study of sitamaquine for the treatment of visceral leishmaniasis in Kenya. Am J Trop Med Hyg 73: 871-876, 2005.
54. Alrajhi AA, Ibrahim EA, De Vol EB, Khairat M, Faris RM and Maguire JH: Fluconazole for the treatment of cutaneous leishmaniasis caused by Leishmania major. N Engl J Med 346: 891-895, 2002.
55. Sundar S, Singh VP, Agrawal NK, Gibbs DL and Murray HW: Treatment of kala-azar with oral fluconazole. Lancet 348: 614, 1996.
56. Roberts CW, McLeod R, Rice DW, Ginger M, Chance ML and Goad LJ: Fatty acid and sterol metabolism: potential antimicrobial targets in apicomplexan and trypanosomatid parasitic protozoa. Mol Biochem Parasitol 126: 129-142, 2003.
57. Croft SL and Yardley V: Chemotherapy of leishmaniasis. Curr Pharm Des 8: 319-342, 2002.
58. Salem MM and Werbovetz KA: Natural products from plants as drug candidates and lead compounds against leishmaniasis and trypanosomiasis. Curr Med Chem 13: 2571-2598, 2006.
59. Kayser O, Kiderlen AF and Croft SL: Natural products as antiparasitic drugs. Parasitol Res 90 (Suppl 2): 55-62, 2003.
60. Rocha LG, Almeida JR, Macedo RO and Barbosa-Filho JM: A review of natural products with antileishmanial activity. Phytomedicine 12: 514-535, 2005.
61. Mittra B, Saha A, Chowdhury AR, et al: Luteolin, an abundant dietary component is a potent anti-leishmanial agent that acts by inducing topoisomerase II-mediated kinetoplast DNA cleavage leading to apoptosis. Mol Med 6: 527-541, 2000.
62. Das BB, Sen N, Roy A, et al: Differential induction of Leishmania donovani bi-subunit topoisomerase I-DNA cleavage complex by selected flavones and camptothecin: activity of flavones against camptothecin-resistant topoisomerase I. Nucleic Acids Res 34: 1121-1132, 2006.
63. Chen M, Christensen SB, Blom J, et al: Licochalcone A, a novel antiparasitic agent with potent activity against human pathogenic protozoan species of Leishmania. Antimicrob Agents Chemother 37: 2550-2556, 1993.
64. Zhai L, Chen M, Blom J, Theander TG, Christensen SB and Kharazmi A: The antileishmanial activity of novel oxygenated chalcones and their mechanism of action. J Antimicrob Chemother 43: 793-803, 1999.
65. Chen M, Christensen SB, Theander TG and Kharazmi A: Antileishmanial activity of licochalcone A in mice infected with Leishmania major and in hamsters infected with Leishmania donovani. Antimicrob Agents Chemother 38: 1339-1344, 1994.
66. Chen M, Zhai L, Christensen SB, Theander TG and Kharazmi A: Inhibition of fumarate reductase in Leishmania major and L. donovani by chalcones. Antimicrob Agents Chemother 45; 2023-2029, 2001.
67. Torres-Santos EC, Moreira DL, Kaplan MA, Meirelles MN and Rossi-Bergmann B: Selective effect of 2′,6′-dihydroxy-4′. methoxychalcone isolated from Piper aduncum on Leishmania amazonensis. Antimicrob Agents Chemother 43: 1234-1241, 1999.
68. Torres-Santos EC, Rodrigues JM Jr, Moreira DL, Kaplan MA and Rossi-Bergmann B: Improvement of in vitro and in vivo antileishmanial activities of 2′, 6′-dihydroxy-4′-methoxychalcone by entrapment in poly (D,L-lactide) nanoparticles, Antimicrob Agents Chemother 43: 1776-1778, 1999.
69. Boeck P, Bandeira Falcao CA, Leal PC, Yunes RA, Filho VC, Torres-Santos EC and Rossi-Bergmann B: Synthesis of chalcone analogues with increased antileishmanial activity. Bioorg Med Chem 14: 1538-1545, 2006.
70. Ray S, Majumder HK, Chakravarty AK, Mukhopadhyay S, Gi1 RR and Cordell GA: Amarogentin, a naturally occurring secoiridoid glycoside and a newly recognized inhibitor of topoisomerase I from Leishmania donovani. J Nat Prod 59: 27-29, 1996.
71. Medda S, Mukhopadhyay S and Basu MK: Evaluation of the in vivo activity and toxicity of amarogentin, an antileishmanial agent, in both liposomal and niosomal forms. J Antimicrob Chemother 44: 791-794, 1999.
72. Fournet A, Angelo A, Munoz V, Roblot F, Hocquemiller R and Cave A: Biological and chemical studies of Pera benensis, a Bolivian plant used in folk medicine as a treatment of cutaneous leishmaniasis. J Ethnopharmacol 37: 159-164, 1992.
73. Hazra B, Sarkar R, Bhattacharyya S, Ghosh PK, Chel G and Dinda B: Synthesis of plumbagin derivatives and their inhibitory activities against Ehrlich ascites carcinoma in vivo and Leishmania donovani promastigotes in vitro. Phytother Res 16: 133-137, 2002.
74. Fournet A, Barrios AA, Munoz V, Hocquemiller R and Cave A: Effect of natural naphthoquinones in BALB/c mice infected with Leishmania amazonensis and L. venezuelensis. Trop Med Parasitol 43: 219-222, 1992.
75. Fujii N, Yamashita Y, Arima Y, Nagashima M and Nakano H: Induction of topoisomerase II-mediated DNA cleavage by the plant naphthoquinones plumbagin and shikonin. Antimicrob Agents Chemother 36: 2589-2594, 1992.
76. Fournet A, Ferreira ME, Rojas De Arias A, et al: In vivo efficacy of oral and intralesional administration of 2-substituted quinolines in experimental treatment of new world cutaneous leishmaniasis caused by Leishmania amazonensis. Antimicrob Agents Chemother 40: 2447-2451, 1996.
77. Fournet A, Gantier JC, Gautheret A, et al: The activity of 2-substituted quinoline alkaloids in BALB/c mice infected with Leishmania donovani. J Antimicrob Chemother 33: 537-544, 1994.
78. Nakayama H, Loiseau PM, Bories C, et al: Efficacy of orally administered 2-substituted quinolines in experimental murine cutaneous and visceral leishmaniases. Antimicrob Agents Chemother 49: 4950-4956, 2005.
79. Germonprez N, Maes L, Van Puyvelde L, Van Tri M, Tuan DA and De Kimpe N: In vitro and in vivo anti-leishmanial activity of triterpenoid saponins isolated from Maesa balansae and some chemical derivatives. J Med Chem 48: 32-37, 2005.
80. Maes L, Vanden Berghe D, Germonprez N, et al: In vitro and in vivo activities of a triterpenoid saponin extract (PX-6518) from the plant Maesa balansae against visceral leishmania species. Antimicrob Agents Chemother 48: 130-136, 2004.
81. Maes L, Germorprez N, Quirijnen L, Van Puyvelde L, Cos P and Vanden Berghe D: Comparative activities of the triterpene saponin maesabalide III and liposomal amphotericin B (AmBisome) against Leishmania donovani in hamsters. Antimicrob Agents Chemother 48: 2056-2060, 2004.
82. Dutta A, Ghoshal A, Mandal D, et al: Racemoside A, an anti-leishmanial, water-soluble, natural steroidal saponin, induces programmed cell death in Leishmania donovani. J Med Microbiol 56: 1196-1204, 2007.
83. Delmas F, Di Giorgio C, Elias R, et al: Antileishmanial activity of three saponins isolated from ivy, alpha-hederin, beta-hederin and hederacolchiside A1, as compared to their action on mammalian cells cultured in vitro. Planta Med 66: 343-347, 2000.
84. Jeong HG and Choi CY: Expression of inducible nitric oxide synthase by alpha-hederin in macrophages. Planta Med 68: 392-396, 2002.
85. Di Giorgio C, Delmas F, Akhmedjanova V, et al: In vitro anti-leishmanial activity of diphyllin isolated from Haplophyllum bucharicum. Planta Med 71: 366-369, 2005.
86. Barata LE, Santos LS, Ferri PH, Phillipson JD, Paine A and Croft SL: Anti-leishmanial activity of neolignans from Virola species and synthetic analogues. Phytochemistry 55: 589-595, 2000.
87. Georgopoulou K, Smirlis D, Bisti S, Xingi E, Skaltsounis L and Soteriadou K: In vitro activity of 10-deacetylbaccatin III against Leishmania donovani promastigotes and intracellular amastigotes. Planta Med 73: 1081-1088, 2007.
88. Sen R, Bandyopadhyay S, Dutta A, et al: Artemisinin triggers induction of cell-cycle arrest and apoptosis in Leishmania donovani promastigotes. J Med Microbiol 56: 1213-1218, 2007.
89. Do Socorro SRMS, Mendonca-Filho RR, Bizzo HR, et al: Antileishmanial activity of a linalool-rich essential oil from Croton cajucara. Antimicrob Agents Chemother 47: 1895-1901, 2003.
90. Di Giorgio C, Lamidi M, Delmas F, Balansard G and Ollivier E: Antileishmanial activity of quinovic acid glycosides and cadambine acid isolated from Nauclea diderrichii. Planta Med 72: 1396-1402, 2006.
91. Brenzan MA, Nakamura CV, Prado Dias Filho B, et al: Antileishmanial activity of crude extract and coumarin from Calophyllum brasiliense leaves against Leishmania amazonensis. Parasitol Res 101: 715-722, 2007.
92. Flores N, Cabrera G, Jimenez IA, et al: Leishmanicidal constituents from the leaves of Piper rusbyi. Planta Med 73: 206-211, 2007.