Drug resistance in plasmodium: Natural products in the fight against malaria

Mini-Reviews in Medicinal Chemistry

Volumn 9, Issue 2, 2009, Pages 206-214

  Turschner, Simon ^a   Efferth, Thomas ^b  

^a UNIVERSITY OF HEIDELBERG   (Germany)

^b GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

Author keywords

Artemisinin; Chemotherapy; Drug resistance; Malaria; Natural products; Pharmacognosy; Plasmodium falciparum

Indexed keywords

AMODIAQUINE; ARTEETHER; ARTEFLENE; ARTEMETHER; ARTEMISININ; ARTESUNATE; ATOVAQUONE; BENFLUMETOL; BRUCEANTIN; CHLOROQUINE; CRYPTOLEPINE; DAPSONE; DIHYDROFOLATE REDUCTASE; DIHYDROPTEROATE SYNTHASE; FANSIDAR; FEBRIFUGINE; HEME; LICOCHALCONE A; MALARIA VACCINE; MANZAMINE A; MEFLOQUINE; NATURAL PRODUCT; PIPERAQUINE; PRIMAQUINE; PROGUANIL; PYRIMETHAMINE; SULFADOXINE; SULFALENE; SULFONE; UNINDEXED DRUG; ANTIMALARIAL AGENT; BIOLOGICAL PRODUCT;

ANTIMALARIAL ACTIVITY; ANTIMALARIAL DRUG RESISTANCE; ARTEMISIA ANNUA; DEVELOPING COUNTRY; DRUG EFFICACY; DRUG HALF LIFE; DRUG METABOLISM; DRUG RESEARCH; DRUG STRUCTURE; ENZYME INHIBITION; HUMAN; INFECTION CONTROL; INHIBITION KINETICS; LIFE CYCLE; MALARIA; MULTIDRUG RESISTANCE; PLASMODIUM FALCIPARUM; POINT MUTATION; POLYMERIZATION; REVIEW; TRADITIONAL MEDICINE; ANIMAL; DRUG EFFECT; DRUG RESISTANCE; PARASITOLOGY; PLASMODIUM;

ANIMALS; ANTIMALARIALS; BIOLOGICAL PRODUCTS; DRUG RESISTANCE; HUMANS; MALARIA; PLASMODIUM;

EID: 65449155546     PISSN: 13895575     EISSN: None     Source Type: Journal    
DOI: 10.2174/138955709787316074     Document Type: Review

References (104)

1. WHO Expert Committee on Malaria: 20th Report (World Health Organization) 2000.
2. Korenromp, E.L. RBM MERG Task Force on Malaria Morbidity: Malaria Incidence Estimates at Country Level for the Year 2004 - Proposed Estimates and Draft Report (World Health Organization, Roll Back Malaria, Geneva) 2005.
3. Sachs, J.; Malaney, P. The economic and social burden of malaria. Nature, 2002, 415, 680-5.
4. Breman, J.G.; Egan, A.; Keusch, G.T. The intolerable burden of malaria: a new look at the numbers. Am. J. Trop. Med. Hyg., 2001, 64, 4-7.
5. Snow, R.W.; Craig, M.; Deichmann, U.; Marsh, K. Estimating mortality, morbidity and disability due to malaria among Africa's non-pregnant population. Bull. World Health Organ., 1999, 77, 624-40.
6. Snow, R.W.; Guerra, C.A.; Noor, A.M.; Myint, H.Y.; Hay, S.I. The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature, 2005, 434, 214-7.
7. Snow, R.W.; Korenromp, E.L.; Gouws, E. Pediatric mortality in Africa: Plasmodium falciparum malaria as a cause or risk? Am. J. Trop. Med. Hyg., 2004, 71, 16-24.
8. Tuteja, R. Malaria - an overview. FEBS J., 2007, 274, 4670-9.
9. Miller, L.H.; Baruch, D.I.; Marsh, K.; Doumbo, O.K. The pathogenic basis of malaria. Nature, 2002, 415, 673-9.
10. Chitnis, C.E.; Blackman, M.J. Host cell invasion by malaria parasites. Parasitol. Today, 2000, 16, 411-5.
11. Bannister, L.H.; Hopkins, J.M.; Fowler, R.E.; Krishna, S.; Mitchell, G.H. A brief illustrated guide to the ultrastructure of Plasmodium falciparum asexual blood stages. Parasitol. Today, 2000, 16, 427-33.
12. Matuschewski, K.; Mueller, A.K. Vaccines against malaria - an update. FEBS J., 2007, 274, 4680-7.
13. Greenwood, D. The quinine connection. J. Antimicrob. Chemother., 1992, 30, 417-27.
14. Yayon, A.; Cabantchik, Z.I.; Ginsburg, H. Identification of the acidic compartment of Plasmodium falciparum-infected human erythrocytes as the target of the antimalarial drug chloroquine. EMBO J., 1984, 3, 2695-700.
15. Foley, M.; Tilley, L. Quinoline antimalarials: mechanisms of action and resistance and prospects for new agents. Pharmacol. Ther., 1998, 79, 55-87.
16. Ginsburg, H.; Ward, S.A.; Bray, P.G. An integrated model of chloroquine action. Parasitol. Today, 1999, 15, 357-60.
17. O'Neill, P.M.; Bray, P.G.; Hawley, S.R.; Ward, S.A.; Park, B.K. 4-Aminoquinolines - past, present, and future: a chemical perspective. Pharmacol. Ther., 1998, 77, 29-58.
18. Macreadie, I.; Ginsburg, H.; Sirawaraporn, W.; Tilley, L. Antimalarial drug development and new targets. Parasitol. Today, 2000, 16, 438-44.
19. Valderramos, S.G.; Fidock, D.A. Transporters involved in resistance to antimalarial drugs. Trends Pharmacol. Sci., 2006, 27, 594-601.
20. Fidock, D.A.; Nomura, T.; Talley, A.K.; Cooper, R.A.; Dzekunov, S.M.; Ferdig, M.T.; Ursos, L.M.; Sidhu, A.B.; Naude, B.; Deitsch, K.W.; Su, X.Z.; Wootton, J.C.; Roepe, P.D.; Wellems, T.E. Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance. Mol. Cell, 2000, 6, 861-71.
21. Bray, P.G.; Martin, R.E.; Tilley, L.; Ward, S.A.; Kirk, K.; Fidock, D.A. Defining the role of PfCRT in Plasmodium falciparum chloroquine resistance. Mol. Microbiol., 2005, 56, 323-33.
22. Cooper, R.A.; Hartwig, C.L.; Ferdig, M.T. pfcrt is more than the Plasmodium falciparum chloroquine resistance gene: a functional and evolutionary perspective. Acta Trop., 2005, 94, 170-80.
23. Cooper, R.A.; Lane, K.D.; Deng, B.; Mu, J.; Patel, J.J.; Wellems, T.E.; Su, X.; Ferdig, M.T. Mutations in transmembrane domains 1, 4 and 9 of the Plasmodium falciparum chloroquine resistance transporter alter susceptibility to chloroquine, quinine and quinidine. Mol. Microbiol., 2007, 63, 270-82.
24. Rohrbach, P.; Sanchez, C.P.; Hayton, K.; Friedrich, O.; Patel, J.; Sidhu, A.B.; Ferdig, M.T.; Fidock, D.A.; Lanzer, M. Genetic linkage of pfmdr1 with food vacuolar solute import in Plasmodium falciparum. EMBO J., 2006, 25, 3000-11.
25. Reed, M.B.; Saliba, K.J.; Caruana, S.R.; Kirk, K.; Cowman, A.F. Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparum. Nature, 2000, 403, 906-9.
26. Babiker, H.A.; Pringle, S.J.; Abdel-Muhsin, A.; Mackinnon, M.; Hunt, P.; Walliker, D. High-level chloroquine resistance in Sudanese isolates of Plasmodium falciparum is associated with mutations in the chloroquine resistance transporter gene pfcrt and the multidrug resistance Gene pfmdr1. J. Infect. Dis., 2001, 183, 1535-8.
27. Djimde, A.; Doumbo, O.K.; Cortese, J.F.; Kayentao, K.; Doumbo, S.; Diourte, Y.; Dicko, A.; Su, X.Z.; Nomura, T.; Fidock, D.A.; Wellems, T.E.; Plowe, C.V.; Coulibaly, D. A molecular marker for chloroquine-resistant falciparum malaria. N. Engl. J. Med., 2001, 344, 257-63.
28. Ngo, T.; Duraisingh, M.; Reed, M.; Hipgrave, D.; Biggs, B.; Cowman, A.F. Analysis of pfcrt, pfmdr1, dhfr, and dhps mutations and drug sensitivities in Plasmodium falciparum isolates from patients in Vietnam before and after treatment with artemisinin. Am. J. Trop. Med. Hyg., 2003, 68, 350-6.
29. Duraisingh, M.T.; Cowman, A.F. Contribution of the pfmdr1 gene to antimalarial drug-resistance. Acta Trop., 2005, 94, 181-90.
30. Sidhu, A.B.; Uhlemann, A.C.; Valderramos, S.G.; Valderramos, J.C.; Krishna, S.; Fidock, D.A. Decreasing pfmdr1 copy number in plasmodium falciparum malaria heightens susceptibility to mefloquine, lumefantrine, halofantrine, quinine, and artemisinin. J. Infect. Dis., 2006, 194, 528-35.
31. Myrick, A.; Munasinghe, A.; Patankar, S.; Wirth, D.F. Mapping of the Plasmodium falciparum multidrug resistance gene 5′-upstream region, and evidence of induction of transcript levels by antimalarial drugs in chloroquine sensitive parasites. Mol. Microbiol., 2003, 49, 671-83.
32. Nelson, A.L.; Purfield, A.; McDaniel, P.; Uthaimongkol, N.; Buathong, N.; Sriwichai, S.; Miller, R.S.; Wongsrichanalai, C.; Meshnick, S.R. pfmdr1 genotyping and in vivo mefloquine resistance on the Thai-Myanmar border. Am. J. Trop. Med. Hyg., 2005, 72, 586-92.
33. Price, R.N.; Uhlemann, A.C.; Brockman, A.; McGready, R.; Ashley, E.; Phaipun, L.; Patel, R.; Laing, K.; Looareesuwan, S.; White, N.J.; Nosten, F.; Krishna, S. Mefloquine resistance in Plasmodium falciparum and increased pfmdr1 gene copy number. Lancet, 2004, 364, 438-47.
34. Baird, J.K.; Hoffman, S.L. Primaquine therapy for malaria. Clin. Infect. Dis., 2004, 39, 1336-45.
35. Egan, T.J. Chloroquine and primaquine: combining old drugs as a new weapon against falciparum malaria? Trends Parasitol., 2006, 22, 235-7.
36. Crabb, B.S. Transfection technology and the study of drug resistance in the malaria parasite Plasmodium falciparum. Drug Resist. Updat., 2002, 5, 126-30.
37. Hyde, J.E. Mechanisms of resistance of Plasmodium falciparum to antimalarial drugs. Microbes Infect., 2002, 4, 165-74.
38. Gregson, A.; Plowe, C.V. Mechanisms of resistance of malaria parasites to antifolates. Pharmacol. Rev., 2005, 57, 117-45.
39. Kublin, J.G.; Dzinjalamala, F.K.; Kamwendo, D.D.; Malkin, E.M.; Cortese, J.F.; Martino, L.M.; Mukadam, R.A.; Rogerson, S.J.; Lescano, A.G.; Molyneux, M.E.; Winstanley, P.A.; Chimpeni, P.; Taylor, T.E.; Plowe, C.V. Molecular markers for failure of sulfadoxine-pyrimethamine and chlorproguanil-dapsone treatment of Plasmodium falciparum malaria. J. Infect. Dis., 2002, 185, 380-8.
40. Sibley, C.H.; Hyde, J.E.; Sims, P.F.; Plowe, C.V.; Kublin, J.G.; Mberu, E.K.; Cowman, A.F.; Winstanley, P.A.; Watkins, W.M.; Nzila, A.M. Pyrimethamine-sulfadoxine resistance in Plasmodium falciparum: what next? Trends Parasitol., 2001, 17, 582-8.
41. McCollum, A.M.; Poe, A.C.; Hamel, M.; Huber, C.; Zhou, Z.; Shi, Y.P.; Ouma, P.; Vulule, J.; Bloland, P.; Slutsker, L.; Barnwell, J.W.; Udhayakumar, V.; Escalante, A.A. Antifolate resistance in Plasmodium falciparum: multiple origins and identification of novel dhfr alleles. J. Infect. Dis., 2006, 194, 189-97.
42. Srivastava, I.K.; Rottenberg, H.; Vaidya, A.B. Atovaquone, a broad spectrum antiparasitic drug, collapses mitochondrial membrane potential in a malarial parasite. J. Biol. Chem., 1997, 272, 3961-6.
43. Fry, M.; Pudney, M. Site of action of the antimalarial hydroxynaphthoquinone, 2-[trans-4-(4′-chlorophenyl) cyclohexyl]-3-hydroxy-1,4-naphthoquinone (566C80). Biochem. Pharmacol., 1992, 43, 1545-53.
44. Mather, M.W.; Darrouzet, E.; Valkova-Valchanova, M.; Cooley, J.W.; McIntosh, M.T.; Daldal, F.; Vaidya, A.B. Uncovering the molecular mode of action of the antimalarial drug atovaquone using a bacterial system. J. Biol. Chem., 2005, 280, 27458-65.
45. Berry, A.; Senescau, A.; Lelievre, J.; Benoit-Vical, F.; Fabre, R.; Marchou, B.; Magnaval, J.F. Prevalence of Plasmodium falciparum cytochrome b gene mutations in isolates imported from Africa, and implications for atovaquone resistance. Trans. R. Soc. Trop. Med. Hyg., 2006, 100, 986-8.
46. Korsinczky, M.; Chen, N.; Kotecka, B.; Saul, A.; Rieckmann, K.; Cheng, Q. Mutations in Plasmodium falciparum cytochrome b that are associated with atovaquone resistance are located at a putative drug-binding site. Antimicrob. Agents Chemother., 2000, 44, 2100-8.
47. Painter, H.J.; Morrisey, J.M.; Mather, M.W.; Vaidya, A.B. Specific role of mitochondrial electron transport in blood-stage Plasmodium falciparum. Nature, 2007, 446, 88-91.
48. Krudsood, S.; Patel, S.N.; Tangpukdee, N.; Thanachartwet, W.; Leowattana, W.; Pornpininworakij, K.; Boggild, A.K.; Looareesuwan, S.; Kain, K.C. Efficacy of atovaquone-proguanil for treatment of acute multidrug-resistant Plasmodium falciparum malaria in Thailand. Am. J. Trop. Med. Hyg., 2007, 76, 655-8.
49. Kuhn, S.; Gill, M.J.; Kain, K.C. Emergence of atovaquoneproguanil resistance during treatment of Plasmodium falciparum malaria acquired by a non-immune north American traveller to west Africa. Am. J. Trop. Med. Hyg., 2005, 72, 407-9.
50. Wichmann, O.; Muehlen, M.; Gruss, H.; Mockenhaupt, F.P.; Suttorp, N.; Jelinek, T. Malarone treatment failure not associated with previously described mutations in the cytochrome b gene. Malar. J., 2004, 3, 14.
51. Hsu, E. Reflections on the 'discovery' of the antimalarial qinghao. Br. J. Clin. Pharmacol., 2006, 61, 666-70.
52. Klayman, D.L. Qinghaosu (artemisinin): an antimalarial drug from China. Science, 1985, 228, 1049-55.
53. Antimalaria studies on Qinghaosu. Chin. Med. J. (Engl.), 1979, 92, 811-6.
54. Krishna, S.; Uhlemann, A.C.; Haynes, R.K. Artemisinins: mechanisms of action and potential for resistance. Drug Resist. Updat., 2004, 7, 233-44.
55. Menard, D.; Matsika-Claquin, M.D.; Djalle, D.; Yapou, F.; Manirakiza, A.; Dolmazon, V.; Sarda, J.; Talarmin, A. Association of failures of seven-day courses of artesunate in a non-immune population in Bangui, Central African Republic with decreased sensitivity of Plasmodium falciparum. Am. J. Trop. Med. Hyg., 2005, 73, 616-21.
56. Olliaro, P.L.; Taylor, W.R. Antimalarial compounds: from bench to bedside. J. Exp. Biol., 2003, 206, 3753-9.
57. Duffy, P.E.; Mutabingwa, T.K. Artemisinin combination therapies. Lancet, 2006, 367, 2037-9.
58. Dokomajilar, C.; Nsobya, S.L.; Greenhouse, B.; Rosenthal, P.J.; Dorsey, G. Selection of Plasmodium falciparum pfmdr1 alleles following therapy with artemether-lumefantrine in an area of Uganda where malaria is highly endemic. Antimicrob. Agents Chemother., 2006, 50, 1893-5.
59. Sisowath, C.; Stromberg, J.; Martensson, A.; Msellem, M.; Obondo, C.; Bjorkman, A.; Gil, J.P. In vivo selection of Plasmodium falciparum pfmdr1 86N coding alleles by artemetherlumefantrine (Coartem). J. Infect. Dis., 2005, 191, 1014-7.
60. Eckstein-Ludwig, U.; Webb, R.J.; Van Goethem, I.D.; East, J.M.; Lee, A.G.; Kimura, M.; O'Neill, P.M.; Bray, P.G.; Ward, S.A.; Krishna, S. Artemisinins target the SERCA of Plasmodium falciparum. Nature, 2003, 424, 957-61.
61. Krishna, S.; Woodrow, C.J.; Staines, H.M.; Haynes, R.K.; Mercereau-Puijalon, O. Re-evaluation of how artemisinins work in light of emerging evidence of in vitro resistance. Trends Mol. Med., 2006, 12, 200-5.
62. Li, W.; Mo, W.; Shen, D.; Sun, L.; Wang, J.; Lu, S.; Gitschier, J.M.; Zhou, B. Yeast model uncovers dual roles of mitochondria in action of artemisinin. PLoS Genet., 2005, 1, e36.
63. Jambou, R.; Legrand, E.; Niang, M.; Khim, N.; Lim, P.; Volney, B.; Ekala, M.T.; Bouchier, C.; Esterre, P.; Fandeur, T.; Mercereau-Puijalon, O. Resistance of Plasmodium falciparum field isolates to in-vitro artemether and point mutations of the SERCA-type PfAT-Pase6. Lancet, 2005, 366, 1960-3.
64. Afonso, A.; Hunt, P.; Cheesman, S.; Alves, A.C.; Cunha, C.V.; do Rosario, V.; Cravo, P. Malaria parasites can develop stable resistance to artemisinin but lack mutations in candidate genes atp6 (encoding the sarcoplasmic and endoplasmic reticulum Ca2+ ATPase), tctp, mdr1, and cg10. Antimicrob. Agents Chemother., 2006, 50, 480-9.
65. Chen, X.; Chong, C.R.; Shi, L.; Yoshimoto, T.; Sullivan, D.J., Jr.; Liu, J.O. Inhibitors of Plasmodium falciparum methionine aminopeptidase 1b possess antimalarial activity. Proc. Natl. Acad. Sci. USA, 2006, 103, 14548-53.
66. Clardy, J.; Walsh, C. Lessons from natural molecules. Nature, 2004, 432, 829-37.
67. Newman, D.J.; Cragg, G.M. Natural products as sources of new drugs over the last 25 years. J. Nat. Prod., 2007, 70, 461-77.
68. Mital, A. Recent advances in antimalarial compounds and their patents. Curr. Med. Chem., 2007, 14, 759-73.
69. Posner, G.H.; Paik, I.H.; Chang, W.; Borstnik, K.; Sinishtaj, S.; Rosenthal, A.S.; Shapiro, T.A. Malaria-infected mice are cured by a single dose of novel artemisinin derivatives. J. Med. Chem., 2007, 50, 2516-9.
70. Vennerstrom, J.L.; Arbe-Barnes, S.; Brun, R.; Charman, S.A.; Chiu, F.C.; Chollet, J.; Dong, Y.; Dorn, A.; Hunziker, D.; Matile, H.; McIntosh, K.; Padmanilayam, M.; Santo Tomas, J.; Scheurer, C.; Scorneaux, B.; Tang, Y.; Urwyler, H.; Wittlin, S.; Charman, W.N. Identification of an antimalarial synthetic trioxolane drug development candidate. Nature, 2004, 430, 900-4.
71. Efferth, T. Willmar Schwabe Award 2006: antiplasmodial and antitumor activity of artemisinin - from bench to bedside. Planta Med., 2007, 73, 299-309.
72. Merali, S.; Meshnick, S.R. Susceptibility of Pneumocystis carinii to artemisinin in vitro. Antimicrob. Agents Chemother., 1991, 35, 1225-7.
73. Sen, R.; Bandyopadhyay, S.; Dutta, A.; Mandal, G.; Ganguly, S.; Saha, P.; Chatterjee, M. Artemisinin triggers induction of cell-cycle arrest and apoptosis in Leishmania donovani promastigotes. J. Med. Microbiol., 2007, 56, 1213-8.
74. Kaptein, S.J.; Efferth, T.; Leis, M.; Rechter, S.; Auerochs, S.; Kalmer, M.; Bruggeman, C.A.; Vink, C.; Stamminger, T.; Marschall, M. The anti-malaria drug artesunate inhibits replication of cytomegalovirus in vitro and in vivo. Antiviral Res., 2006, 69, 60-9.
75. Romero, M.R.; Efferth, T.; Serrano, M.A.; Castano, B.; Macias, R.I.; Briz, O.; Marin, J.J. Effect of artemisinin/artesunate as inhibitors of hepatitis B virus production in an "in vitro" replicative system. Antiviral Res., 2005, 68, 75-83.
76. Wright, C.W.; Addae-Kyereme, J.; Breen, A.G.; Brown, J.E.; Cox, M.F.; Croft, S.L.; Gokcek, Y.; Kendrick, H.; Phillips, R.M.; Pollet, P.L. Synthesis and evaluation of cryptolepine analogues for their potential as new antimalarial agents. J. Med. Chem., 2001, 44, 3187-94.
77. Dassonneville, L.; Bonjean, K.; De Pauw-Gillet, M.C.; Colson, P.; Houssier, C.; Quetin-Leclercq, J.; Angenot, L.; Bailly, C. Stimulation of topoisomerase II-mediated DNA cleavage by three DNA-intercalating plant alkaloids: cryptolepine, matadine, and serpentine. Biochemistry, 1999, 38, 7719-26.
78. Wright, C.W. Recent developments in naturally derived antimalarials: cryptolepine analogues. J. Pharm. Pharmacol., 2007, 59, 899-904.
79. Jonckers, T.H.; van Miert, S.; Cimanga, K.; Bailly, C.; Colson, P.; De Pauw-Gillet, M.C.; van den Heuvel, H.; Claeys, M.; Lemiere, F.; Esmans, E.L.; Rozenski, J.; Quirijnen, L.; Maes, L.; Dommisse, R.; Lemiere, G.L.; Vlietinck, A.; Pieters, L. Synthesis, cytotoxicity, and antiplasmodial and antitrypanosomal activity of new neocryptolepine derivatives. J. Med. Chem., 2002, 45, 3497-508.
80. Schindler, F.; Zahner, H. Metabolic products of microorganisms. 91. Tryptanthrin, a tryptophan derived antibiotic from Candida lipolytica. Arch. Mikrobiol., 1971, 79, 187-203.
81. Danz, H.; Stoyanova, S.; Wippich, P.; Brattstrom, A.; Hamburger, M. Identification and isolation of the cyclooxygenase-2 inhibitory principle in Isatis tinctoria. Planta Med., 2001, 67, 411-6.
82. Bhattacharjee, A.K.; Hartell, M.G.; Nichols, D.A.; Hicks, R.P.; Stanton, B.; van Hamont, J.E.; Milhous, W.K. Structure-activity relationship study of antimalarial indolo [2,1-b]quinazoline-6,12-diones (tryptanthrins). Three dimensional pharmacophore modeling and identification of new antimalarial candidates. Eur. J. Med. Chem., 2004, 39, 59-67.
83. Valiente, N. Use of tryptanthrin compounds for immune potentiation. WO2004064759. Patent, 2004.
84. Francois, G.; Timperman, G.; Eling, W.; Assi, L.A.; Holenz, J.; Bringmann, G. Naphthylisoquinoline alkaloids against malaria: evaluation of the curative potentials of dioncophylline C and dioncopeltine A against Plasmodium berghei in vivo. Antimicrob. Agents Chemother., 1997, 41, 2533-9.
85. Schwedhelm, K.F.; Horstmann, M.; Faber, J.H.; Reichert, Y.; Bringmann, G.; Faber, C. The novel antimalarial compound dioncophylline C forms a complex with heme in solution. ChemMed-Chem, 2007, 2, 541-548.
86. Ang, K.K.; Holmes, M.J.; Higa, T.; Hamann, M.T.; Kara, U.A. In vivo antimalarial activity of the beta-carboline alkaloid manzamine A. Antimicrob. Agents Chemother., 2000, 44, 1645-9.
87. Hill, R.; Hamann, M.T.; Peraud, O.; Kasanah, N. Manzamine-producing actinomycetes. WO2004013297. Patent. 2006.
88. Hirai, S.; Kikuchi, H.; Kim, H.S.; Begum, K.; Wataya, Y.; Tasaka, H.; Miyazawa, Y.; Yamamoto, K.; Oshima, Y. Metabolites of febrifugine and its synthetic analogue by mouse liver S9 and their antimalarial activity against Plasmodium malaria parasite. J. Med. Chem., 2003, 46, 4351-9.
89. Carraz, M.; Jossang, A.; Franetich, J.F.; Siau, A.; Ciceron, L.; Hannoun,L.; Sauerwein, R.; Frappier, F.; Rasoanaivo, P.; Snounou, G.; Mazier, D. A plant-derived morphinan as a novel lead compound active against malaria liver stages. PLoS Med., 2006, 3, e513.
90. Rasoanaivo, P.; Ratsimamanga-Urverg, S.; Milijaona, R.; Rafatro, H.; Rakoto-Ratsimamanga, A.; Galeffi, C.; Nicoletti, M. In vitro and in vivo chloroquine-potentiating action of Strychnos myrtoides alkaloids against chloroquine-resistant strains of Plasmodium malaria. Planta Med., 1994, 60, 13-6.
91. Rafatro, H.; Ramanitrahasimbola, D.; Rasoanaivo, P.; Ratsimamanga-Urverg, S.; Rakoto-Ratsimamanga, A.; Frappier, F. Reversal activity of the naturally occurring chemosensitizer malagashanine in Plasmodium malaria. Biochem. Pharmacol., 2000, 59, 1053-61.
92. Ramanitrahasimbola, D.; Rasoanaivo, P.; Ratsimamanga, S.; Vial, H. Malagashanine potentiates chloroquine antimalarial activity in drug resistant Plasmodium malaria by modifying both its efflux and influx. Mol. Biochem. Parasitol., 2006, 146, 58-67.
93. Posner, G.H.; Cumming, J.N.; Woo, S.H.; Ploypradith, P.; Xie, S.; Shapiro, T.A. Orally active antimalarial 3-substituted trioxanes: new synthetic methodology and biological evaluation. J. Med. Chem., 1998, 41, 940-51.
94. Wright, A.D.; Konig, G.M.; Angerhofer, C.K.; Greenidge, P.; Linden, A.; Desqueyroux-Faundez, R. Antimalarial activity: the search for marine-derived natural products with selective antimalarial activity. J. Nat. Prod., 1996, 59, 710-6.
95. Angerhofer, C.K.; Pezzuto, J.M.; Konig, G.M.; Wright, A.D.; Sticher, O. Antimalarial activity of sesquiterpenes from the marine sponge Acanthella klethra. J. Nat. Prod., 1992, 55, 1787-9.
96. Wright, A.D.; Wang, H.; Gurrath, M.; Konig, G.M.; Kocak, G.; Neumann, G.; Loria, P.; Foley, M.; Tilley, L. Inhibition of heme detoxification processes underlies the antimalarial activity of terpene isonitrile compounds from marine sponges. J. Med. Chem., 2001, 44, 873-85.
97. Trager, W.; Polonsky, J. Antimalarial activity of quassinoids against chloroquine-resistant Plasmodium falciparum in vitro. Am. J. Trop. Med. Hyg., 1981, 30, 531-7.
98. Anderson, M.M.; O'Neill, M.J.; Phillipson, J.D.; Warhurst, D.C. In vitro cytotoxicity of a series of quassinoids from Brucea javanica fruits against KB cells. Planta Med., 1991, 57, 62-4.
99. Muhammad, I.; Bedir, E.; Khan, S.I.; Tekwani, B.L.; Khan, I.A.; Takamatsu, S.; Pelletier, J.; Walker, L.A. A new antimalarial quassinoid from Simaba orinocensis. J. Nat. Prod., 2004, 67, 772-7.
100. Murakami, N.; Sugimoto, M.; Kawanishi, M.; Tamura, S.; Kim, H.S.; Begum, K.; Wataya, Y.; Kobayashi, M. New semisynthetic quassinoids with in vivo antimalarial activity. J. Med. Chem., 2003, 46, 638-41.
101. Chen, M.; Theander, T.G.; Christensen, S.B.; Hviid, L.; Zhai, L.; Kharazmi, A. Licochalcone A, a new antimalarial agent, inhibits in vitro growth of the human malaria parasite Plasmodium falciparum and protects mice from P. yoelii infection. Antimicrob. Agents Chemother., 1994, 38, 1470-5.
102. Dominguez, J.N.; Leon, C.; Rodrigues, J.; Gamboa de Dominguez, N.; Gut, J.; Rosenthal, P.J. Synthesis and evaluation of new antimalarial phenylurenyl chalcone derivatives. J. Med. Chem., 2005, 48, 3654-8.
103. Wu, X.; Wilairat, P.; Go, M.L. Antimalarial activity of ferrocenyl chalcones. Bioorg. Med. Chem. Lett., 2002, 12, 2299-302.
104. Xue, C.X.; Cui, S.Y.; Liu, M.C.; Hu, Z.D.; Fan, B.T. 3D QSAR studies on antimalarial alkoxylated and hydroxylated chalcones by CoMFA and CoMSIA. Eur. J. Med. Chem., 2004, 39, 745-53.