Artemisinins: Mechanisms of action and potential for resistance

Drug Resistance Updates

Volumn 7, Issue 4-5, 2004, Pages 233-244

  Krishna, Sanjeev ^a   Uhlemann, Anne Catrin ^a   Haynes, Richard K ^b  

^a ST GEORGE'S UNIVERSITY OF LONDON   (United Kingdom)

^b HONG KONG UNIVERSITY OF SCIENCE AND TECHNOLOGY   (Hong Kong)

Author keywords

Artemisinin; Endoperoxides; Malaria; Plasmodium falciparum

Indexed keywords

10 DEOXOARTEMISININ; AMINOQUINOLINE DERIVATIVE; AMODIAQUINE; ANTIMALARIAL AGENT; ARTEETHER; ARTEMETHER; ARTEMISININ DERIVATIVE; ARTESUNATE; ATOVAQUONE; DIHYDROARTEMISININ; FERROUS ION; FOLIC ACID ANTAGONIST; MEFLOQUINE; PEROXIDE; QUININE; TERT BUTYL HYDROPEROXIDE; UNCLASSIFIED DRUG;

ANTIMALARIAL ACTIVITY; DNA POLYMORPHISM; DRUG MECHANISM; HUMAN; HYPERINSULINEMIA; HYPOGLYCEMIA; MALARIA; MULTIDRUG RESISTANCE; NONHUMAN; PLASMODIUM FALCIPARUM; PRIORITY JOURNAL; REVIEW;

EID: 7944222115     PISSN: 13687646     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.drup.2004.07.001     Document Type: Article

References (100)

1. M. Adjuik, P. Agnamey, and A. Babiker Amodiaquine-artesunate versus amodiaquine for uncomplicated Plasmodium falciparum malaria in African children: a randomised, multicentre trial Lancet 359 2002 1365 1372
2. M. Adjuik, A. Babiker, P. Garner, P. Olliaro, W. Taylor, and N. White Artesunate combinations for treatment of malaria: meta-analysis Lancet 363 2004 9 17
3. T. Agbenyega, B. Angus, and G. Bedu-Addo Glucose and lactate kinetics in children with severe malaria J. Clin. Endocrinol. Metab. 85 2000 1569 1576
4. M.H. Alin, M. Ashton, C.M. Kihamia, G.J.B. Mtey, and A. Bjorkman Multiple dose pharmacokinetics of oral artemisinin and comparison of its efficacy with that of oral artesunate in falciparum malaria patients Trans. R. Soc. Trop. Med. Hyg. 90 1996 61 65
5. B.J. Angus, K. Chotivanich, R. Udomsangpetch, and N.J. White In vivo removal of malaria parasites from red blood cells without their destruction in acute falciparum malaria Blood 90 1997 2037 2040
6. W. Asawamahasakda, I. Ittarat, Y.M. Pu, H. Ziffer, and S.R. Meshnick Reaction of antimalarial endoperoxides with specific parasite proteins Antimicrob. Agents Chemother. 38 1994 1854 1858
7. M.A. Avery, W.K.M. Chong, and J.E. Bupp Tricyclic analogues of artemisinin: synthesis and antimalarial activity of (+)-4,5-secoartemisinin and (-)-5-nor-4,5-secoartemisinin J. Chem. Soc. Chem. Commun. 1990 1487 1489
8. M.A. Avery, F. Gao, W.K.M. Chong, S. Mehrotra, and W.K. Milhous Structure-activity relationships of the antimalarial agent artemisinin. 1. Synthesis and comparative molecular field analysis of C-9 analogs of artemisinin and 10-deoxoartemisinin J. Med. Chem. 36 1993 4264 4275
9. M.A. Avery, F. Gao, W.K.M. Chong, T.F. Hendrickson, W.D. Inman, and P. Crews Synthesis, conformational analysis, and antimalarial activity of tricyclic analogues of artemisinin Tetrahedron 50 1994 952 957
10. M.A. Avery, P. Fan, J.M. Karle, J.D. Bonk, R. Miller, and D.K. Goins Structure-activity relationships of the antimalarial agent artemisinin 3. Total synthesis of (+)-13-carbaartemisinin and related tetra- and tricyclic structures J. Med. Chem. 39 1996 1885 1897
11. M.A. Avery, S. Mehrotra, T.L. Johnson, J.D. Bonk, J.A. Vroman, and R. Miller Structure-activity relationships of the antimalarial agent artemisinin 5. Analogs of 10-deoxoartemisinin substituted at C-3 and C-9 J. Med. Chem. 39 1996 4149 4155
12. M.A. Avery, M. Alvim-Gaston, and C.R. Rodrigues Structure-activity relationships of the antimalarial agent artemisinin 6. The development of predictive in vitro potency models using CoMFA and HQSAR methodologies J. Med. Chem. 45 2002 292 303
13. J. Bhisutthibhan, X.Q. Pan, and P.A. Hossler The Plasmodium falciparum translationally controlled tumor protein homolog and its reaction with the antimalarial drug artemisinin J. Biol. Chem. 273 1998 16192 16198
14. A.R. Butler, B.C. Gilbert, P. Hulme, L.R. Irvine, L. Renton, and A.C. Whitwood EPR evidence for the involvement of free radicals in the iron-catalysed decomposition of qinghaosu (artemisinin) and some derivatives; antimalarial action of some polycyclic endoperoxides Free Radic. Res. 28 1998 471 476
15. I.A. Clark, N.H. Hunt, W.B. Cowden, L.E. Maxwell, and E.J. Mackie Radical-mediated damage to parasites and erythrocytes in Plasmodium vinckei infected mice after injection of t-butyl hydroperoxide Clin. Exp. Immunol. 56 1984 524 530
16. Clennan, E.L., Foote, C.S. 1992. In: Ando, W. (Ed.), Organic Peroxides. Wiley, Chichester, pp. 295-304.
17. A.F. Cowman, D. Galatis, and J.K. Thompson Selection for mefloquine resistance in Plasmodium falciaprum is linked to amplification of the pfmdr1 gene and cross-resistance to halofantrine and quinine Proc. Natl. Acad. Sci. U.S.A. 91 1994 114 114
18. Davies, A.G., 1961. Organic Peroxides. Butterworths, London, pp. 174-179.
19. M.J. Dobson Bitter-sweet solutions for malaria: exploring natural remedies from the past Parassitologia 40 1998 69 81
20. U. Eckstein-Ludwig, R. Webb, I.D. Van Geothem, J.M. East, A.G. Lee, M. Kimura, P.M. O'Neill, P.G. Bray, S.A. Ward, and S. Krishna Artemisinins target the SERCA of Plasmodium falciparum Nature 424 2003 957 961
21. T.J. Egan, J.M. Combrinck, and J. Egan Fate of haem iron in the malaria parasite Plasmodium falciparum Biochem. J. 365 2002 343 347
22. D. Greenwood The quinine connection J. Antimicrob. Chemother. 30 1992 417 427
23. Halliwell, B., Gutteridge, J.M.C., 1999. Free Radicals in Biology and Medicine. Clarendon Press, Oxford, pp. 140-142 (Chapter 3).
24. Halliwell, B., Gutteridge, J.M.C., 1999. Free Radicals in Biology and Medicine. Clarendon Press, Oxford, pp. 140-142 (Chapter 3).
25. R.K. Haynes Artemisinin and derivatives: the future for malaria treatment? Curr. Opin. Infect. Dis. 14 2001 719 726
26. R.K. Haynes, and S.C. Vonwiller The behaviour of qinghaosu in the presence of non-heme iron(II) and (III) Tetrahedron Lett. 37 1996 257 260
27. R.K. Haynes, and S.C. Vonwiller The behaviour of qinghaosu (artemisinin) in the presence of heme iron (II) and (III) Tetrahedron Lett. 37 1996 253 256
28. R.K. Haynes, H.-O. Pai, and A. Voerste Ring opening of artemisinin (qinghaosu) and dihydroartemisinin and interception of the open hydroperoxides with formation of N-oxides - a chemical model for antimalarial mode of action Tetrahedron Lett. 40 1999 4715 4718
29. R.K. Haynes, D. Monti, D. Taramelli, N. Basilico, S. Parapini, and P. Olliaro Artemisinin antimalarials do not inhibit hemozoin formation Antimicrob. Agents Chemother. 47 2003 1175
30. R.K. Haynes, W.-Y. Ho, and H.-W. Chan Highly antimalaria-active artemisinin derivatives: biological activity does not correlate with chemical reactivity Angew. Chem. Int. Ed. 43 2004 138 138
31. T.T. Hien An overview of the clinical use of artemisinin and its derivatives in the treatment of falciparum malaria in Viet Nam Trans. R. Soc. Trop. Med. Hyg. 88 Suppl. 1 1994 S7 S8
32. T.T. Hien, and N.J. White Qinghaosu Lancet 341 1993 603 608
33. T.T. Hien, D. Tam, N. Cuc, and K. Arnold Comparative effectiveness of artemisinin suppositories and oral quinine in children with acute falciparum malaria Trans. R. Soc. Trop. Med. Hyg. 85 1991 210 211
34. S. Hindley, S.A. Ward, and R.C. Storr Mechanism-based design of parasite-targeted artemisinin derivatives: synthesis and antimalarial activity of new diamine containing analogues J. Med. Chem. 45 2002 1052 1063
35. Y.L. Hong, Y.Z. Yang, and S.R. Meshnick The interaction of artemisinin with malarial hemozoin Mol. Biochem. Parasitol. 63 1994 121 128
36. - channels of human erythrocytes by membrane oxidation EMBO J. 21 2002 1 9
37. N.H. Hunt, and R. Stocker Oxidative stress and the redox status of malaria-infected erythrocytes Blood Cells 16 1990 499 526 discussion 527-530
38. M. Jung, X. Li, D.A. Bustos, H.N. elSohly, J.D. McChesney, and W.K. Milhous Synthesis and antimalarial activity of (+)-deoxoartemisinin J. Med. Chem. 33 1990 1516 1518
39. S. Kamchonwongpaisan, P. Mckeever, P. Hossler, H. Ziffer, and S.R. Meshnick Artemisinin neurotoxicity: neuropathology in rats and mechanistic studies in vitro Am. J. Trop. Med. Hyg. 56 1997 7 12
40. D.L. Klayman Qinghaosu (artemisinin): an antimalarial drug from China Science 228 1985 1049 1055
41. D.L. Klayman, A.J. Lin, and N. Acton Isolation of artemisinin (qinghaosu) from artemisia annua growing in the United States J. Nat. Prod. 47 1984 715 717
42. M. Korsinczky, N. Chen, B. Kotecka, A. Saul, K. Rieckmann, and Q. Cheng Mutations in Plasmodium falciparum cytochrome b that are associated with atovaquone resistance are located at a putative drug-binding site Antimicrob. Agents Chemother. 44 2000 2100 2108
43. P.G. Kremsner, and S. Krishna Antimalarial combinations Lancet 364 2004 285 294
44. S. Krishna, T. Planche, and T. Agbenyega Bioavailability and preliminary clinical efficacy of intrarectal artesunate in Ghanaian children with moderate malaria Antimicrob. Agents Chemother. 45 2001 509 516
45. Y. Li, and Y.L. Wu An over four millennium story behind qinghaosu (artemisinin) - a fantastic antimalarial drug from a traditional Chinese herb Curr. Med. Chem. 10 2003 2197 2307
46. A.-J. Lin, D.L. Klayman, J.M. Hoch, J.V. Silverton, and C.F. George Thermal rearrangement and decomposition products of artemisinin (qinghaosu) J. Org. Chem. 50 1985 4504 4508
47. S. Matsugo, and I. Saito W. Ando Organic Peroxides 1992 Wiley Chichester 174 179
48. S. Matsugo, and I. Saito W. Ando Organic Peroxides 1992 Wiley Chichester 178 179
49. S.R. Meshnick, A. Thomas, A. Ranz, C.M. Xu, and H.Z. Pan Artemisinin (qinghaosu): the role of intracellular hemin in its mechanism of antimalarial action Mol. Biochem. Parasitol. 49 1991 181 189
50. S.A. Murphy, E. Mberu, and D. Muhia The disposition of intramuscular artemether in children with cerebral malaria; a preliminary study Trans. R. Soc. Trop. Med. Hyg. 91 1997 331 334
51. C. Nealon, A. Dzeing, and U. Muller-Romer Intramuscular bioavailability and clinical efficacy of artesunate in Gabonese children with severe malaria Antimicrob. Agents Chemother. 46 2002 3933 3939
52. P. Newton, Y. Suputtamongkol, and P. Teja-Isavadharm Antimalarial bioavailability and disposition of artesunate in acute falciparum malaria Antimicrob. Agents Chemother. 44 2000 972 977
53. N. Ningsanont, D.S. Black, R. Chanphen, and Y. Thebtaranonth Synthesis of ethyl 5-phenyl-6-oxa-1-azabicyclo[3.1.0]hexane-2-carboxylate derivatives and evaluation of their antimalarial activities J. Med. Chem. 46 2003 2397 2403
54. A. Nontprasert, S. Pukrittayakamee, A.M. Dondorp, R. Clemens, S. Looareesuwan, and N.J. White Neuropathologic toxicity of artemisinin derivatives in a mouse model Am. J. Trop. Med. Hyg. 67 2002 423 429
55. F. Nosten, F. ter Kuile, and T. Chongsuphajaisiddhi Mefloquine-resistant falciparum malaria on the Thai-Burmese border Lancet 337 1991 1140 1143
56. F. Nosten, M. van Vugt, and R. Price Effects of artesunate-mefloquine combination on incidence of Plasmodium falciparum malaria and mefloquine resistance in western Thailand: a prospective study Lancet 356 2000 297 302
57. P.L. Olliaro, and W.R. Taylor Developing artemisinin based drug combinations for the treatment of drug resistant falciparum malaria: a review J. Postgrad. Med. 50 2004 40 44
58. P.L. Olliaro, R.K. Haynes, B. Meunier, and Y. Yuthavong Possible modes of action of the artemisinin-type compounds Trends Parasitol. 17 2001 122 126
59. P.L. Olliaro, R.K. Haynes, B. Meunier, and Y. Yuthavong Radical mechanism of action of the artemisinin-type compounds. Reply to comments Trends Parasitol. 17 2001 267 268
60. P.M. O'Neill, A. Miller, and L.P. Bishop Synthesis, antimalarial activity, biomimetic iron(II) chemistry, and in vivo metabolism of novel, potent C-10-phenoxy derivatives of dihydroartemisinin J. Med. Chem. 44 2001 58 68
61. S. Pagola, P.W. Stephens, D.S. Bohle, A.D. Kosar, and S.K. Madsen The structure of malaria pigment beta-haematin Nature 404 2000 307 310
62. A.V. Pandey, B.L. Tekwani, R.L. Singh, and V.S. Chauhan Artemisinin, an endoperoxide antimalarial, disrupts the hemoglobin catabolism and heme detoxification systems in malarial parasite J. Biol. Chem. 274 1999 19383 19388
63. V. Papalexis, M.A. Siomos, and N. Campanale Histidine-rich protein 2 of the malaria parasite, Plasmodium falciparum, is involved in detoxification of the by-products of haemoglobin degradation Mol. Biochem. Parasitol. 115 2001 77 86
64. N.A. Porter W. Ando Organic Peroxides 1992 Wiley Chichester 139 142
65. G.H. Posner, and C.H. Oh A regiospecifically oxygen-18 labeled 1,2,4-trioxane: a simple chemical model to probe the mechanism(s) for the antimalarial activity of artemisinin (qinghaosu) J. Am. Chem. Soc. 114 1992 8328 8329
66. G.H. Posner, and P.M. O'Neill Knowledge of the proposed chemical mechanism of action and cytochrome p450 metabolism of antimalarial trioxanes like artemisinin allows rational design of new antimalarial peroxides Acc. Chem. Res. 37 2004 397 404
67. G.H. Posner, J.N. Cumming, P. Ploypradith, and C.H. Oh Evidence for Fe(IV)O in the molecular mechanism of action of the trioxane antimalarial artemisinin J. Am. Chem. Soc. 117 1995 5885 5886
68. N.S. Postma, E.C. Mommers, W.M. Eling, and J. Zuidema Oxidative stress in malaria; implications for prevention and therapy Pharm. World Sci. 18 1996 121 129
69. R.N. Price, F. Nosten, and C. Luxemburger Effects of artemisinin derivatives on malaria transmissibility Lancet 347 1996 1654 1658
70. R. Price, C.A. Cassar, and A. Brockman Pfmdr1 gene amplification and multidrug resistant Plasmodium falciparum on the north west border of Thailand Antimicrobial. Agents Chemother. 43 1999 2943 2949
71. R. Price, A.C. Uhlemann, A. Brockman, R. McGready, E. Ashley, L. Phaipun, R. Patel, K. Laing, S. Looareesuwan, N.J. White, F. Nosten, and S. Krisha Mefloquine resistance in Plasmodium falciparum results from increased pfmdr1 gene copy number Lancet 364 2004 438 447
72. Qinghaosu C-ORGo, 1977. Kuo Xue Tung Bao 22, 142.
73. Qinghaosu C-ORGo, 1979. Antimalaria studies on Qinghaosu. Chin. Med. J. (Engl.) 92, 811-816.
74. P.K. Rathod, T. McErlean, and P.-C. Lee Variations in frequencies of drug resistance in Plasmodium falciparum Proc. Natl. Acad. Sci. U.S.A. 94 1997 9389 9393
75. A. Robert, and B. Meunier Characterization of the first covalent adduct between artemisinin and a heme model J. Am. Chem. Soc. 119 1997 5968
76. A. Robert, and B. Meunier Alkylating properties of antimalarial artemisinin derivatives and synthetic trioxanes when activated by a reduced heme model Chem. Eur. J. 4 1998 1287
77. A. Robert, J. Cazelles, and B. Meunier Characterization of the alkylation product of heme by the antimalarial drug artemisinin Angew Chem. Int. Ed. Engl. 40 2001 1954 1957
78. A. Robert, O. Dechy-Cabaret, J. Cazelles, and B. Meunier From mechanistic studies on artemisinin derivatives to new modular antimalarial drugs Acc. Chem. Res. 35 2002 167 174
79. I. Saito, and S.S. Nittala The Chemistry of the Functional Group S. Patai Peroxides vol. 33 1983 Wiley New York 356 365
80. G. Sosnovsky, and D.J. Rawlinson D. Swern Organic Peroxides vol. 1 1971 Wiley Interscience New York 561 566
81. G. Sosnovsky, and D.J. Rawlinson D. Swern Organic Peroxides vol. 2 1971 Wiley Interscience New York
82. D.J. Sullivan Theories on malarial pigment formation and quinoline action Int. J. Parasitol. 32 2002 1645 1653
83. F.O. ter Kuile, N.J. White, P.A. Holloway, G. Pasvol, and S. Krishna Plasmodium falciparum: in vitro studies of the pharmacodynamic properties of antimalarials used for the treatment of severe malaria Exp. Parasitol. 76 1993 85 95
84. R. Udomsangpetch, B. Pipitaporn, and S. Krishna Antimalarial drugs reduce cytoadherence and rosetting of Plasmodium falciparum J. Infect. Dis. 173 1996 691 698
85. J.L. Vennerstrom, N. Acton, A.J. Lin, and D.L. Klayman Peroxides as oxidant antimalarials Drug Des. Deliv. 4 1989 45 54
86. L. von Seidlein, G. Walraven, and P.J.M. Milligan The effect of mass administration of sulfadoxine-pyrimethamine combined with artesunate on malaria incidence: a double-blind, communit-randomized, placebo controlled trial in The Gambia Trans. R. Soc. Trop. Med. Hyg. 97 2003 129 256
87. D.-Y. Wang, and Y.-L. Wu A possible antimalarial action mode of qinghaosu (artemisinin) series compounds. Alkylation of reduced glutathione by C-centered primary radicals produced from antimalarial compound qinghaosu and 12-(2,4-dimethoxyphenyl)-12-deoxoqinghaosu J. Chem. Soc. Chem. Commun. 2000 219 219
88. N.J. White Preventing antimalarial drug resistance through combinations Drug Resistance Update 1 1998 3 9
89. N.J. White Delaying antimalarial drug resistance with combination chemotherapy Parassitologia 41 1999 301 308
90. N.J. White Antimalarial drug resistance and combination chemotherapy Philos. Trans. R. Soc. B 354 1999 739 749
91. N.J. White, D.A. Warrell, and P. Chantavanich Severe hypoglycaemia and hyperinsulinaemia in falciparum malaria N. Engl. J. Med. 309 1983 61 66
92. P.A. Winstanley, S.A. Ward, and R.W. Snow Clinical status and implications of antimalarial drug resistance Microbes Infect. 4 2002 157 164
93. Y. Wu How might qinghaosu (artemisinin) and related compounds kill the intraerythrocytic malaria parasite? A chemist's view Acc. Chem. Res. 35 2002 255 259
94. W.M. Wu, Y. Wu, and Y.L. Wu Unified mechanistic framework for the Fe(II)-induced cleavage of qinghaosu and derivatives/analogues. The first spin trapping evidence for the previously postulated secondary C-4 radical J. Am. Chem. Soc. 120 1998 3316 3325
95. Y.-K. Wu, Z.-Y. Wu, and Y.-L. Wu Interaction of qinghaosu (artemisinin) with cysteine sulfhydryl mediated by traces of non-heme iron Angew. Chem. Int. Ed. Engl. 38 1999 2580 2582
96. Y.-K. Wu, Z.-Y. Yue, and H.-H. Liu Helv. Chim. Acta 84 2001 928 932
97. W.-M. Wu, Y.-L. Chen, Z. Zhai, S.-H. Xiao, and Y.-L. Wu Study on the mechanism of action of artemether against schistosomes: the identification of cysteine adducts of both carbon-centred free radicals derived from artemether Bioorg. Med. Chem. Lett. 13 2003 1645 1647
98. B. Ye, and Y.-L. Wu Synthesis of carba-analogues of Qinghaosu Tetrahedron 45 1989 7287 7290
99. B. Ye, Y.L. Wu, G.F. Li, and X.Q. Jiao Antimalarial activity of deoxoqinghaosu Yao Xue Xue Bao 26 1991 228 230
100. F. Zhang, D.K. Gosser Jr., and S.R. Meshnick Hemin-catalyzed decomposition of artemisinin (qinghaosu) Biochem. Pharmacol. 43 1992 1805 1809