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Pharmacological Potential of Natural Compounds in the Control of Selected Protozoan Diseases

  • Gabriela HrckovaEmail author
  • Samuel Velebny
Chapter
Part of the SpringerBriefs in Pharmaceutical Science & Drug Development book series (BRIEFSPSDD)

Abstract

Malaria, trypanosomiasis, and leishmaniasis (neglected tropical diseases), belong to the most devastating diseases affecting humans and animals in developing regions of Asia, Africa, and South America. The drugs, currently used for the treatment of these diseases, are mostly effective; however, some of them have limitations, such as toxic side effects and high cost. Moreover, Plasmodium, Trypanosoma, and Leishmania have developed resistance to many of these drugs. In the first part of this chapter, problems of pathology, therapy, and drug resistance are reviewed. The following part focuses on plants, bacteria, fungi, and marine organisms, which provide invaluable sources of compounds with antiparasitic potential. The compounds isolated from nature are classified according to their chemical structure, and methods for evaluation of their antiparasitic activity are also discussed. The review of promising results, obtained by many investigators from the year 2000 by screening of natural compounds evaluating their antiplasmodial, trypanocidal, and leishmanicidal activity, are presented in the last three parts of this chapter.

Keywords

Malaria Trypanosomiasis Leishmaniasis Pathology Current drugs Drug resistance Drug discovery Higher plants Marine organisms Secondary metabolites Screening of natural compounds 

References

  1. Ang KKH, Holmes MJ, Higa T, Hamann MT, Kara UAK (2000) In vivo antimalarial activity of the beta-carboline alkaloid manzamine A. Antimicrob Agents Chemother 44(6):1645–1649. doi:  10.1128/AAC.44.6.1645-1649.2000 Google Scholar
  2. Anthony JP, Fyfe L, Smith H (2005) Plant active components—a resource for antiparasitic agents? Trends Parasitol 21:462–468. doi: 10.1016/j.pt.2005.08.004 PubMedCrossRefGoogle Scholar
  3. Arruda DC, D’Alexandri FL, Katzin AM, Uliana SRB (2005) Antileishmanial activity of the terpene nerolidol. Antimicrob Agents Chemother 48:1679–1687. doi:  10.1128/AAC.49.5.1679-1687.2005 Google Scholar
  4. Barret MP, Vincent IM, Burchmore RJ, Kazibwe AJ, Matovu E (2011) Drug resistance in human African trypanosomiasis. Future Microbiol 6(9):1037–1047. doi: 10.2217/fmb.11.88 CrossRefGoogle Scholar
  5. Blumenstiel K, Schoneck R, Yardley V, Croft SL, Krauth-Siegel RL (1999) Nitrofuran drugs as common subversive substrates of Trypanosoma cruzi lipoamide dehydrogenase and trypanothione reductase. Biochem Pharmacol 58:1791–1799Google Scholar
  6. Brenzan MA, Nakamura CV, Prado Dias Filho B et al (2007) Antileishmanial activity of crude extract and coumarin from Calophyllum brasiliense leaves against Leishmania amazonensis. Parasitol Res 101:715–722. doi:  10.1007/s00436-007-0542-7
  7. Burleigh BA, Woolsey AM (2002) Cell signaling and Trypanosoma cruzi invasion. Cell Microbiol 4:701–711Google Scholar
  8. Byadgi PS (2011) Natural products and their antileishmanial activity. A critical review. Int Res J Pharm 2:46–49. http://www.irjponline.com Google Scholar
  9. Carvalho PB, Ferreira EI (2001) Leishmaniasis phytotherapy. Nature′s leadership against an ancient disease—review. Fitoterapia 72:599–618Google Scholar
  10. Chan-Bacab MJ, Peña-Rodríguez LM (2001) Plant natural products with leishmanicidal activity. Nat Prod Rep 18:674–688. doi: 10.1039/B100455G PubMedCrossRefGoogle Scholar
  11. Chawla B, Madhubala R (2010) Drug targets in Leishmania. J Parasit Dis 34:1–13. doi: 10.1007/s12639-010-0006-3 PubMedCrossRefGoogle Scholar
  12. Chen M, Zhai L, Christensen SB, Theander TG, Kharazmi A (2001) Inhibition of fumarate reductase in Leishmania major and L. donovani by chalcones. Antimicrob Agents Chemother 45:2023–2029. doi: 10.1128/AAC.45.7.2023-2029.2001 PubMedCrossRefGoogle Scholar
  13. Copp RB, Kayser O, Brun R, Kiderlen AF (2003) Antiparasitic activity of marine pyridoacridone alkaloids related to the ascididemins. Planta Med 69:527–531. doi: 10.1055/s-2003-40640 PubMedGoogle Scholar
  14. Coppi A, Cabinian M, Mirelman D, Sinnis P (2006) Antimalarial activity of allicin, a biologically active compound from garlic cloves. Antimicrob Agents Chemother 50:1731–1737. doi: 10.1128/AAC.50.5.1731-1737.2006 PubMedCrossRefGoogle Scholar
  15. Croft SL, Sundar S, Fairlamb AH (2006) Drug resistance in leishmaniasis. Clin Microbiol Rev 19(1):111–126. doi:  10.1128/CMR.19.1.111–126.2006 Google Scholar
  16. Cui L, Miao J, Cui L (2007) Cytotoxic effect of curcumin on malaria parasite Plasmodium falciparum: inhibition of histone acetylation and generation of reactive oxygen species. Antimicrob Agents Chemother 51(2):488–494. doi: 10.1128/AAC.01238-06 PubMedCrossRefGoogle Scholar
  17. Cunha WR, dos Santos FM, Peixoto JA, Veneziani RCS, Crotti AEM, Silva MLA, Filho AAS, Albuquerque S, Turatti ICC, Bastos JK (2009) Screening of plant extracts from the Brazilian Cerrado for their in vitro trypanocidal activity. Pharm Biol (formerly Int J Pharmacognosy) 47:744–749. doi: http://dx.doi.org/10.1080/13880200902951361 Google Scholar
  18. Das A, Dasgupta A, Sengupta T, Majumder HK (2004) Topoisomerases of kinetoplastid parasites as potential chemotherapeutic targets. Trends Parasitol 20:381–387. doi: 10.1016/j.pt.2004.06.005 PubMedCrossRefGoogle Scholar
  19. Das BB, Sen N, Roy A, Dasgupta SB, Ganguly A, Mohanta BC, Dinda B, Majumder HK (2006) 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. doi: 10.1093/nar/gkj502 PubMedCrossRefGoogle Scholar
  20. de Carvalho PB, Ferreira EI (2001) Leishmaniasis phytotherapy. Nature’s leadership against an ancient disease. Fitoterapia 72:599–618Google Scholar
  21. de Monbrison F, Maitrejean M, Latour Ch, Bugnazet F, Peyron F, Barron D, Staphane P (2006) In vitro antimalarial activity of flavonoid derivatives dehydrosilybin and 8-(1,1)-DMA-kaempferide. Acta Tropica 97:102–107 Google Scholar
  22. Delmas F, Di Giorgio C, Elias R et al (2000) 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. doi: 10.1055/s-2000-8541 PubMedCrossRefGoogle Scholar
  23. Di Giorgio C, Delmas F, Akhmedjanova V et al (2005) In vitro antileishmanial activity of diphyllin isolated from Haplophyllum bucharicum. Planta Med 71:366–369Google Scholar
  24. Do Socorro SRMS, Mendonca-Filho RR, Bizzo HR et al (2003) Antileishmanial activity of a linalool-rich essential oil from Croton cajucara. Antimicrob Agents Chemother 47:1895–1901. doi:  10.1128/AAC.47.6.1895-1901.2003
  25. Dua VK, Verma G, Agarwal DD, Kaiser M, Brun R (2011) Antiprotozoal activities of traditional medicinal plants from the Garhwal region of North West Himalaya, India. J Ethnopharmacol 136:123–128. doi:  10.1016/j.jep.2011.04.024 Google Scholar
  26. Eckstein-Ludwig U, Webb RJ, Van Goethem ID, East JM, Lee AG, Kimura M, O’Neill PM, Bray PG, Ward SA, Krishna S (2003) Artemisinins target the SERCA of Plasmodium falciparum. Nature 424:957–961Google Scholar
  27. Fattorusso E, Taglialatela-Scafati O (2009) Marine antimalarials. Mar Drugs 7:130–152. doi: 10.3390/md7020130 PubMedCrossRefGoogle Scholar
  28. Frederich M, Tits M, Angenot L (2008) Potential antimalarial activity of indole alkaloids. Trans R Soc Trop Med Hyg 102:11–19. doi: 10.1016/j.trstmh.2007.10.002 PubMedCrossRefGoogle Scholar
  29. Fröhlich S, Schubert C, Bienzle U, Jenett-Siems K (2005) In vitro antiplasmodial activity of prenylated chalcone derivatives of hops (Humulus lupulus) and their interaction with haemin. J Antimicrob Chemother 55:883–887. doi: 10.1093/jac/dki099 CrossRefGoogle Scholar
  30. Gehrig S, Efferth T (2008) Development of drug resistance in Trypanosoma brucei rhodensiense and Trypanosoma brucei gambiense. Treatment of human African trypanosomiasis with natural products (Review). Int J Mol Med 22:411–419. doi: 0.3892/ijmm_00000037PubMedGoogle Scholar
  31. Gelb MH (2007) Drug discovery for malaria: a very challenging and timely endeavor. Curr Opin Chem Biol 11:440–445. doi: 10.1016/j.cbpa.2007.05.038 Google Scholar
  32. Goulart HR, Kimura EA, Peres VJ, Couto AS, Duarte FAA, Katzin AM (2004) Terpenes arrest parasite development and inhibit biosynthesis of isoprenoids in Plasmodium falciparum. Antimicrob Agents Chemother 48:2502–2509. doi:  10.1128/AAC.48.7.2502–2509.2004
  33. Hoet S, Opperdoes F, Brun R, Quetin-Leclercq J (2004) Natural products active against African trypanosomes: a step towards new drugs. Nat Prod Rep 21:353–364Google Scholar
  34. Jeong HG, Choi CY (2002) Expression of inducible nitric oxide synthase by alpha-hederin in macrophages. Planta Med 68:392–396Google Scholar
  35. Kaur K, Jain M, Kaur T, Jain R (2009): Antimalarials from nature. Bioorg Med Chem 17:3229–3256Google Scholar
  36. Kayser O, Kiderlen AF, Bertels S, Siems K (2001) Antileishmanial activities of aphidicolin and its semisynthetic derivatives. Antimicrob Agents Chemother 45:288–292. doi: 10.1128/AAC.45.1.288-292.2001 PubMedCrossRefGoogle Scholar
  37. Kayser O, Kiderlen AF, Croft SL (2002) Natural products as potential antiparasitic drugs. In Studies in Natural Product Chemistry 26, pp 779–848. Elsevier, UK. http://userpage.fu-berlin.de/~kayser/antiparasiticsfromnature.pdf
  38. Kayser O, Kiderlen AF, Croft SL (2003) Natural products as antiparasitic drugs. Parasitol Res 90:S55–S62. doi: 10.1007/s00436-002-0768-3 PubMedCrossRefGoogle Scholar
  39. Kothari H, Kumar P, Sundar S, Singh N (2007) Possibility of membrane modification as a mechanism of antimony resistance in Leishmania donovani. Parasitol Int 56(1):77–80. http://dx.doi.org/10.1016/j.parint.2006.10.005 Google Scholar
  40. Laport MS, Santos OCS, Muricy G (2009) Marine sponges: potential sources of new antimicrobial drugs. Curr Pharm Biotechnol 10:86–105Google Scholar
  41. Laurent D, Pietra F (2006) Antiplasmodial marine natural products in the perspective of current chemotherapy and prevention of malaria. A review. Mar Biotechnol 8:433–447. doi: 10.1007/s10126-006-6100-y PubMedCrossRefGoogle Scholar
  42. Laurent D, Jullian V, Parenty A, Knibiehler M, Dorin D, Schmitt S, Lozach O, Lebouvier N, Frostin M, Alby F, Maurel S, Doerig C, Meijerf M, Sauvain M (2006) Antimalarial potential of xestoquinone, a protein kinase inhibitor isolated from a Vanuatu marine sponge Xestospongia sp. Bioorg Med Chem 14:4477–4482. doi: 10.1016/j.bmc.2006.02.026 PubMedCrossRefGoogle Scholar
  43. Le Pape P, Zidane M, Abdala H, Moré MT (2000) A glycoprotein isolated from the sponge, Pachymatisma johnstonii, has anti-leishmanial activity. Cell Biol Int 24:51–56. doi: 10.1006/cbir.1999.0450 PubMedCrossRefGoogle Scholar
  44. Lopes NP, Kato MJ, Andrade EH, Maia JG, Yoshida M, Planchart AR, Katzin AM (1999) Antimalarial use of volatile oil from leaves of Virola surinamensis (Rol.) Warb. by Waiapi Amazon Indians. J Ethnopharmacol 67:313–319. http://dx.doi.org/10.1016/S0378-8741(99)00072-0 Google Scholar
  45. Ma Y, Lu DM, Lu XJ, Lia L, Hu XS (2004) Activity of dihydroartemisinin against Leishmania donovani both in vitro and in vivo. Chin Med J 117:1271–1273Google Scholar
  46. Malebo HM, Tanja W, Cal M, Swaleh SAM, Omolo MO, Hassanali A, Séquin U, Hamburger M, Brun R, Ndiege IO (2009) Antiplasmodial, anti-trypanosomal, anti-leishmanial and cytotoxicity activity of selected Tanzanian medicinal plants. Tanzan J Health Res 11(4):2266–2234Google Scholar
  47. Maltezou HC (2010) Drug resistance in visceral leishmaniasis. J Biomed Biotechnol 2010:617521. doi:  10.1155/2010/617521
  48. Maya JD, Cassels BK, Iturriaga-Vásquez P, Ferreira J, Faúndez M, Galanti N, Ferreira A, Morello A (2007) Mode of action of natural and synthetic drugs against Trypanosoma cruzi and their interaction with the mammalian host. Comp Biochem Physiol Part A 146:601–620. doi: 10.1016/j.cbpa.2006.03.004 CrossRefGoogle Scholar
  49. Mendiola J, Hernández H, Sariego I, Rojas L, Otero A, Ramírez A, Chávez MA, Payrol JA (2006) Antimalarial activity from three ascidians: an exploration of different marine invertebrate phyla. Trans R Soc Trop Med Hyg 100:909–915. doi: 10.1016/j.trstmh.2005.11.013 PubMedCrossRefGoogle Scholar
  50. Mishina YV, Krishna S, Haynes RK, Meade JC (2007) Artemisinins inhibit Trypanosoma cruzi and Trypanosoma brucei rhodesiense in vitro growth. Animicrob Agents Chemother 51(5):1852–1854. doi: 10.1128/AAC.01544-06 CrossRefGoogle Scholar
  51. Mittal MK, Rai S, Ravinger A, Gupta S, Sundar S, Goyal N (2007) Characterization of natural antimony resistance in Leishmania donovani isolates. Am J Trop Med Hyg 76(4):681–688Google Scholar
  52. Mittra B, Saha A, Chowdhury AR et al (2000) 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 6:527–541Google Scholar
  53. Mizuno Y, Makioka A, Kawazu S, Kano S, Kawai S, Akaki M, Aikawa M, Ohtomo H (2002) Effect of jasplakinolide on the growth, invasion, and actin cytoskeleton of Plasmodium falciparum. Parasitol Res 88:844–848. doi: 10.1007/s00436-002-0666-8 PubMedCrossRefGoogle Scholar
  54. Monzote L (2009) Current treatment of leishmaniasis: a review. Open Antimicrob Agents J 1:9–19Google Scholar
  55. Muhammad I, Bedir E, Khan SI, Tekwani BL, Khan IA, Takamatsu S, Pelletier J, Walker LA (2004) A new antimalarial quassinoid from Simaba orinocensis. J Nat Prod 67:772–777Google Scholar
  56. Mukherjee A, Padmanabhan PK, Singh S et al (2007) Role of ABC transporter MRPA, γ-glutamylcysteine synthetase and ornithine decarboxylase in natural antimony-resistant isolates of Leishmania donovani. J Antimicrob Chemother 59(2):204–211. doi: 10.1093/jac/dkl494 PubMedCrossRefGoogle Scholar
  57. Muthaura CN, Rukunga GM, Chhabra SC, Omar SA, Guantai AN, Gathirwa JW, Tolo FM, Mwitari PG, Keter LK, Kirira PG, Kimani CW, Mungai GM, Njagi EN (2007) Antimalarial activity of some plants traditionally used in Meru district of Kenya. Phytother Res 21:860–867. doi: 10.1002/ptr.2170 PubMedCrossRefGoogle Scholar
  58. Muthaura CN, Keriko JM, Derese S, Yenesew A, Rukunga GM (2011) Investigation of some medicinal plants traditionally used for the treatment of malaria in Kenya as potential sources of antmalarial drugs. Exp Parasitol 127:609–626. doi: 10.1016/j.exppara.2010.11.004 PubMedCrossRefGoogle Scholar
  59. Mwangi ESK, Keriko JM, Machocho AK, Wanyonyi AW, Malebo HM, Chhabra SC, Tarus PK (2010) Antiprotozoal activity and cytotoxicity of metabolites from leaves of Teclea trichocarpa. J Med Plants Res 4(9):726–731. doi: 10.5897/JMPR09.188 Google Scholar
  60. Plock A, Sokolowska-Köhler W, Presber W (2001) Application of flow cytometry and microscopical methods to characterize the effect of herbal drugs on Leishmania spp. Exp Parasitol 97:141–153. doi: 10.1006/expr.2001 PubMedCrossRefGoogle Scholar
  61. Polonio T, Efferth T (2008) Leishmaniasis: drug resistance and natural products (Review). Int J Mol Med 22:277–286Google Scholar
  62. Rocha LG, Almeida JRGS, Macedo RO, Barbosa-Filho JM (2005) A review of natural products with antileishmanial activity. Phytomedicine 12:514–535. doi: 10.1016/j.phymed.2003.10 PubMedCrossRefGoogle Scholar
  63. Rosa MSS, Mendonça-Filho RR, Bizzo HR, de Almeida RI, Soares RM, Souto-Padrón T, Alviano CS, Lopes AH (2003) Antileishmanial activity of linalool-rich essential oil from Croton cajucara. Antimicrob Agents Chemother 47:1895–1901. doi: 10.1128/AAC.47.6.1895-1901.2003 CrossRefGoogle Scholar
  64. Salas C, Tapia RA, Ciudad K, Armstrong V, Orellana M, Kemmerling U, Ferreira J, Maya JD, Morello A (2008) Trypanosoma cruzi: activities of lapachol and alpha- and beta-lapachone derivatives against epimastigote and trypomastigote forms. Bioorg Med Chem 16:668–674Google Scholar
  65. Salas CO, Faúndez M, Morello A, Maya JD, Tapia RA (2011) Natural and synthetic naphthoquinones active against Trypanosoma Cruzi: an initial step towards new drugs for Chagas disease. Curr Med Chem 18:144–161Google Scholar
  66. Salem MM, Werbovetz KA (2006) Natural products from plants as drug candidates and lead compounds against leishmaniasis and trypanosomias. Curr Med Chem 13:2571–2598Google Scholar
  67. Sanchez AM, Jimenez-Ortiz V, Sartor T, Tonn CE, García EE, Nieto M, Burgos MH, Sosa MA (2006) A novel icetexane diterpene, 5-epi-icetexone from Salvia gilliessi is active against Trypanosoma cruzi. Acta Trop 98:118–124. doi: 10.1016/j.actatropica.2005.12.007 PubMedCrossRefGoogle Scholar
  68. Saxena S, Pant N, Jain DC, Bhakuni RS (2006) Antimalarial agents from plant sources. Curr Sci 85:1314–1329Google Scholar
  69. Schmidt TJ, Brun R, Willuhn G, Khalid SA (2002) Anti-trypanosomal activity of helenalin and some structurally related sesquiterpene lactones. Planta Med 68:750–751. doi: 10.1055/s-2002-33799 PubMedCrossRefGoogle Scholar
  70. Schmidt TJ, Khalid SA, Romanha AJ, Alves TM, Biavatti MW, Brun R, Da Costa FB, de Castro SL, Ferreira VF, de Lacerda MV, Lago JH, Leon LL, Lopes NP, das Neves Amorim RC, Niehues M, Ogungbe IV, Pohlit AM, Scotti MT, Setzer WN, de N C Soeiro M, Steindel M, Tempone AG (2012a) The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases—part I. Curr Med Chem 19:2128–2175Google Scholar
  71. Schmidt TJ, Khalid SA, Romanha AJ, Alves TM, Biavatti MW, Brun R, Da Costa FB, de Castro SL, Ferreira VF, de Lacerda MV, Lago JH, Leon LL, Lopes NP, das Neves Amorim RC, Niehues M, Ogungbe IV, Pohlit AM, Scotti MT, Setzer WN, de N C Soeiro M, Steindel M, Tempone AG (2012b) The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases—part II. Curr Med Chem 19:2176–2228Google Scholar
  72. Steverding D, Tyler KM (2005) Novel antitrypanosomal agents. Expert Opin Investig Drugs 14:939–955. doi: 10.1517/13543784.14.8.939 PubMedCrossRefGoogle Scholar
  73. Taleb-Contini SH, Salvador MJ, Balanco JMF, Albuquerque S, de Oliveira DCR (2004) Antiprotozoal effect of crude extracts and flavonoids isolated from Chromolaena hirsuta (Asteraceae). Phytother Res 18:250–254. doi: 10.1002/ptr.1431 PubMedCrossRefGoogle Scholar
  74. Tasdemir D, Brun R, Perozzo R, Dönmez AA (2005) Evaluation of antiprotozoal and plasmodial enoyl-ACP reductase inhibition potential of Turkish medicinal plants. Phytother Res 19:162–166. doi: 10.1002/ptr.1648 PubMedCrossRefGoogle Scholar
  75. Tasdemir D, Kaiser M, Brun R,Yardley V, Schmidt TJ, Tosun F, Rüedi P (2006) 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 50:1352–1364. doi:  10.1128/AAC.50.4.1352-1364.2006 Google Scholar
  76. Taylor WR, White NJ (2004) Antimalarial drug toxicity: a review. Drug Saf 27:25–61Google Scholar
  77. Tempone AG, Sartorelli P, Teixeira D, Prado FO, Calixto IARL, Lorenzi H, Melhem MSC (2008) Brazilian flora extracts as source of novel antileishmanial and antifungal compounds. Mem Inst Oswaldo Cruz 103:443–449Google Scholar
  78. Thomas TRA, Kavlekar DP, LokaBharathi PA (2010) Marine drugs from sponge-microbe association—a review. Mar Drugs 8:1417–1468. doi: 10.3390/md8041417 PubMedCrossRefGoogle Scholar
  79. van Agtmael MA, Eggelte TA, van Boxtel SJ (1999) Artemisinin drugs in the treatment of malaria: from medicinal herb to registered medication. Trends Pharmacol Sci 20:199–205. doi: 10.1016/S0165-6147(99)01302-4 PubMedCrossRefGoogle Scholar
  80. Varughese G, Sabulal B, Anil J (2010) Ethnomedicinal plants in parasitic infections. In: Chattopadhyay D (ed) Ethnomedicine: a source of complementary therapeutics, pp 53–116, ISBN 978-81-308-0390-6Google Scholar
  81. Vonthron-Sénécheau C, Weniger B, Ouattara M, Tra Bi F, Kamenan A, Lobstein A, Brun R, Anton R (2003) In vitro antiplasmodial activity and cytotoxicity of ethnobotanically selected Ivorian plants. J Ethnopharmacol 87:221–225. doi:  10.1016/S0378-8741(03)00144-2 Google Scholar
  82. Weiss CR, Moideen SVK, Simon L, Croft SL, Peter J, Houghton PJ (2000) Activity of extracts and isolated naphthoquinones from Kigelia pinnata against Plasmodium falciparum. J Nat Prod 63(9):1306–1309. doi:  10.1021/np000029g
  83. White NJ (2004) Antimalarial drug resistance. J Clin Invest 113:1084–1092. doi: 10.1172/JCI200421682 PubMedGoogle Scholar
  84. WHO (2001) Antimalarial drug combination therapy: report of a WHO technical consultation. In WHO/CDS/RBM, vol 2001.35. World Health Organization, GenevaGoogle Scholar
  85. WHO (2002) The world health report 2002: reducing risks, promoting healthy life. World Health Organization, GenevaGoogle Scholar
  86. Wilkinson SR, Kelly JM (2009) Trypanocidal drugs: mechanisms, resistance and new targets. Expert Rev Mol Med 11:1–31. doi: http://dx.doi.org/10.1017/S1462399409001252 Google Scholar
  87. Wong IL, Chan K-F, Burkett BA et al (2007) Flavonoid dimers as bivalent modulators for pentamidine and sodium stiboglucanate resistance in Leishmania. Antimicrob Agents Chemother 51(3):930–940. doi:  10.1128/AAC.00998-06
  88. Woodrow CJ, Haynes RK, Krishna S (2005) Artemisinins. Postgrad Med J 81:71–78. doi: 10.1136/pgmj.2004.028399 PubMedCrossRefGoogle Scholar
  89. Woster PM (2009) Principles of pharmacotherapy 3: infectious diseases and disease of the respiratory tract. In Chemistry of antiparasitic agents. http://www.acsmedchem.org/module/antiparasitic.html
  90. Wright CW (2005) Traditional antimalarials and the development of novel antimalarial drugs. J Ethnopharmacol 100:67–71. doi:  10.1016/j.jep.2005.05.012 Google Scholar
  91. Wright AD, Papendorf O, Konig GM (2005) Ambigol C and 2,4-dichlorobenzoic acid, natural products produced by the terrestrial cyanobacterium Fischerella ambigua. J Nat Prod 68:459–461. doi: 10.1021/np049640w PubMedCrossRefGoogle Scholar
  92. Yabu Y, Yoshida A, Suzuki T et al (2003) The efficacy of ascufuranone in a consecutive treatment on Trypanosoma brucei brucei in mice. Parasitol Int 52:155–164. doi: 10.1016/S1383-5769(03)00012-6 PubMedCrossRefGoogle Scholar
  93. Zhang L, An R, Wang J, Sun N, Zhang S, Hu J, Kuai J (2005) Exploring novel bioactive compounds from marine microbes. Curr Opin Microbiol 8:276–281. doi: 10.1016/j.mib.2005.04.008 PubMedCrossRefGoogle Scholar
  94. Ziegler HL, Hansen HS, Stœrk D, Christensen SB, Hägerstrand H, Jaroszewski JW (2004) The antiparasitic compound licochalcone A is a potent echinocytogenic agent that modifies the erythrocyte membrane in the concentration range where antiplasmodial activity is observed. Antimicrob Agents Chemother 48:4067–4071. doi: 10.1128/AAC.48.10.4067-4071.2004 PubMedCrossRefGoogle Scholar

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© The Author(s) 2013

Authors and Affiliations

  1. 1.Slovak Academy of SciencesInsitute of ParasitologyKosiceSlovakia

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