Artemisinin: mechanisms of action, resistance and toxicity

Adams, 1996, Reaction between ferriprotoporphyrin IX and the antimalarial endoperoxide artesunate gives an intermediate species with enhanced redox catalytic activity, J. Pharm. Pharmacol., 48, 183, 10.1111/j.2042-7158.1996.tb07119.x

Antimalarials, 1972, Chemical studies on qinghaosu (artemisinine), J. Tradit. Chin. Med., 2, 3

Asawamahasakda, 1994, Effects of antimalarials and protease inhibitors on plasmodial hemozoin production, Mol. Biochem. Parasitol., 67, 183, 10.1016/0166-6851(94)00128-6

Asawamahasakda, 1994, Reaction of antimalarial endoperoxides with specific parasite proteins, Antimicrob. Agents Chemother., 38, 1854, 10.1128/AAC.38.8.1854

Avery, 2002, 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, 292, 10.1021/jm0100234

Bachi, 2000, Synthesis and reactions of antimalarial bicyclic peroxides, J. Heterocycl. Chem., 37, 639, 10.1002/jhet.5570370321

Benoit-Vical, 2000, In vitro and in vivo potentiation of artemisinin and synthetic endoperoxide antimalarial drugs by metalloporphyrins [In Process Citation], Antimicrob. Agents Chemother., 44, 2836, 10.1128/AAC.44.10.2836-2841.2000

Berman, 1997, Artemisinin enhances heme-catalysed oxidation of lipid membranes, Free Radic. Biol. Med., 22, 1283, 10.1016/S0891-5849(96)00508-4

Bharel, 1998, Artemisinin mediated alteration of haemin to a delta-meso oxidation product: relevance to mechanism of action, J. Chem. Soc. Perkin Trans., 1, 2163, 10.1039/a802423e

Bhisutthibhan, 2001, Immunoprecipitation of [(3)H]dihydroartemisinin translationally controlled tumor protein (TCTP) adducts from Plasmodium falciparum-infected erythrocytes by using anti-TCTP antibodies, Antimicrob. Agents Chemother., 45, 2397, 10.1128/AAC.45.8.2397-2399.2001

Bhisutthibhan, 1998, The Plasmodium falciparum translationally controlled tumor protein homolog and its reaction with the antimalarial drug artemisinin, J. Biol. Chem., 273, 16192, 10.1074/jbc.273.26.16192

Bhisutthibhan, 1999, The Plasmodium falciparum translationally controlled tumor protein: subcellular localization and calcium binding, Eur. J. Cell Biol., 78, 665, 10.1016/S0171-9335(99)80052-1

Brewer, 1998, Factors relating to neurotoxicity of artemisinin antimalarial drugs ‘listening to arteether’, Med. Trop. (Mars), 58, 22

Brossi, 1988, Arteether, a new antimalarial drug: synthesis and antimalarial properties, J. Med. Chem., 31, 645, 10.1021/jm00398a026

Butler, 1998, 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, 471, 10.3109/10715769809066884

Cazelles, 2002, Alkylating capacity and reaction products of antimalarial trioxanes after activation by a heme model, J. Org. Chem., 67, 609, 10.1021/jo010688d

Chen, 1994, The infectivity of gametocytes of Plasmodium falciparum from patients treated with artemisinin, Chin. Med. J. (Engl.), 107, 709

Chotivanich, 2000, The mechanisms of parasite clearance after antimalarial treatment of Plasmodium falciparum malaria, J. Infect. Dis., 182, 629, 10.1086/315718

Cooper, 2002, Alternative mutations at position 76 of the vacuolar transmembrane protein PfCRT are associated with chloroquine resistance and unique stereospecific quinine and quinidine responses in Plasmodium falciparum, Mol. Pharmacol., 61, 35, 10.1124/mol.61.1.35

Dayan, 1998, Neurotoxicity and artemisinin compounds do the observations in animals justify limitation of clinical use?, Med. Trop. (Mars), 58, 32

Duraisingh, 2000, Increased sensitivity to the antimalarials mefloquine and artemisinin is conferred by mutations in the pfmdr1 gene of Plasmodium falciparum, Mol. Microbiol., 36, 955, 10.1046/j.1365-2958.2000.01914.x

Dutta, 1989, Artemisinin (qinghaosu) – a new gametocytocidal drug for malaria, Chemotherapy, 35, 200, 10.1159/000238671

Ellis, 1985, The chemotherapy of rodent malaria, Ann. Trop. Med. Parasitol., 79, 367, 10.1080/00034983.1985.11811933

Fishwick, 1998, Morphological and immunocytochemical effects of dihydroartemisinin on differentiating NB2a neuroblastoma cells, Neurotoxicology, 19, 393

Fishwick, 1995, The toxicity of artemisinin and related compounds on neuronal and glial cells in culture, Chem. Biol. Interact., 96, 263, 10.1016/0009-2797(94)03597-2

Geary, 1989, Stage specific actions of antimalarial drugs on Plasmodium falciparum in culture, Am. J. Trop. Med. Hyg., 40, 240, 10.4269/ajtmh.1989.40.240

Gogtay, 2000, Probable resistance to parenteral artemether in Plasmodium falciparum: case reports from Mumbai (Bombay), India, Ann. Trop. Med. Parasitol., 94, 519, 10.1080/00034983.2000.11813571

Gu, 1999, The radical transformation in artemisinin: a DFT study, J. Phys. Chem., 103, 9364, 10.1021/jp992577c

Halliwell, 1999

Haynes, 1999, 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, 15, 10.1016/S0040-4039(99)00830-8

Haynes, 1996, The behaviour of quinghaosu(artemisinin) in the presence of heme iron(II) and (III), Tetrahedron Lett., 37, 253, 10.1016/0040-4039(95)02141-8

Hong, 1994, The interaction of artemisinin with malarial hemozoin, Mol. Biochem. Parasitol., 63, 121, 10.1016/0166-6851(94)90014-0

Inselburg, 1985, Induction and isolation of artemisinine-resistant mutants of Plasmodium falciparum, Am. J. Trop. Med. Hyg., 34, 417, 10.4269/ajtmh.1985.34.417

Jefford, 1995, The decomposition of cis-fused cyclopenteno-1,2,4-trioxanes induced by ferrous salts and some oxophilic reagents, Helv. Chim. Acta, 78, 452, 10.1002/hlca.19950780216

Jiang, 1985, Qinghaosu-induced changes in the morphology of Plasmodium inui, Am. J. Trop. Med. Hyg., 34, 424, 10.4269/ajtmh.1985.34.424

Kamchonwongpaisan, 1997, Artemisinin neurotoxicity: neuropathology in rats and mechanistic studies in vitro, Am. J. Trop. Med. Hyg., 56, 7, 10.4269/ajtmh.1997.56.7

Kapetanaki, 2000, Ferryl-oxo heme intermediate in the antimalarial mode of action of artemisinin, FEBS Lett., 474, 238, 10.1016/S0014-5793(00)01592-1

Krungkrai, 1987, The antimalarial action on Plasmodium falciparum of qinghaosu and artesunate in combination with agents which modulate oxidant stress, Trans. R. Soc. Trop. Med. Hyg., 81, 710, 10.1016/0035-9203(87)90003-4

Kumar, 1990, Stage-specific gametocytocidal effect in vitro of the antimalaria drug qinghaosu on Plasmodium falciparum, Parasitol. Res., 76, 214, 10.1007/BF00930817

Le Bras, 1998, In vitro susceptibility of African Plasmodium falciparum isolates to dihydroartemisinin and the risk factors for resistance to qinghaosu, Med. Trop. (Mars), 58, 18

Levander, 1989, Qinghaosu, dietary vitamin E, selenium, and cod-liver oil: effect on the susceptibility of mice to the malarial parasite Plasmodium yoelii, Am. J. Clin. Nutr., 50, 346, 10.1093/ajcn/50.2.346

Luxemburger, 1998, Two patients with falciparum malaria and poor in vivo responses to artesunate, Trans. R. Soc. Trop. Med. Hyg., 92, 668, 10.1016/S0035-9203(98)90807-0

Maeno, 1993, Morphologic effects of artemisinin in Plasmodium falciparum, Am. J. Trop. Med. Hyg., 49, 485, 10.4269/ajtmh.1993.49.485

McGready, 1998, Artemisinin derivatives in the treatment of falciparum malaria in pregnancy, Trans. R. Soc. Trop. Med. Hyg., 92, 430, 10.1016/S0035-9203(98)91081-1

McIntosh, H., Olliaro., P., 1999. Artemisinin derivatives for treating severe malaria. Cochrane Database of Systematic Reviews.

McIntosh, H., Olliaro., P.,1999. Artemisinin derivatives for treating uncomplicated malaria. Cochrane Database of Systematic Reviews.

Meshnick, 1998, From quinine to qinghaosu: historical perspectives, 341

Meshnick, 2001, The history of antimalarial drugs. Antimalarial chemotherapy, 15

Meshnick, 1991, Artemisinin (qinghaosu): the role of intracellular hemin in its mechanism of antimalarial action, Mol. Biochem. Parasitol., 49, 181, 10.1016/0166-6851(91)90062-B

Meshnick, 1989, Activated oxygen mediates the antimalarial activity of qinghaosu, Prog. Clin. Biol. Res., 313, 95

Meshnick, 1993, Iron-dependent free radical generation from the antimalarial agent artemisinin (qinghaosu), Antimicrob. Agents Chemother., 37, 1108, 10.1128/AAC.37.5.1108

Miller, 1997, Ataxia and slurred speech after artesunate treatment for falciparum malaria [letter] [see comments], N. Engl. J. Med., 336, 1328, 10.1056/NEJM199705013361818

Nontprasert, 1998, Assessment of the neurotoxicity of parenteral artemisinin derivatives in mice, Am. J. Trop. Med. Hyg., 59, 519, 10.4269/ajtmh.1998.59.519

Nontprasert, 2000, Studies of the neurotoxicity of oral artemisinin derivatives in mice, Am. J. Trop. Med. Hyg., 62, 409, 10.4269/ajtmh.2000.62.409

Nosten, 1998, Use of artemisinin derivatives for the control of malaria, Med. Trop. (Mars), 58, 45

Nosten, 2000, Effects of artesunate–mefloquine combination on incidence of Plasmodium falciparum malaria and mefloquine resistance in western Thailand: a prospective study, Lancet, 356, 297, 10.1016/S0140-6736(00)02505-8

O'Neill, 1997, The biomimetic iron-mediated degradation of Arteflene (Ro-42-1611), an endoperoxide antimalarial – implications for the mechanism of antimalarial activity, Tetrahedron Lett., 38, 4263, 10.1016/S0040-4039(97)00874-5

Paitayatat, 1997, Correlation ofantimalarial activity of artemisinin derivatives with binding affinity with ferroprotoporphyrin IX, J. Med. Chem., 40, 633, 10.1021/jm960767v

Pandey, 1999, Artemisinin, an endoperoxide antimalarial, disrupts the hemoglobin catabolism and heme detoxification systems in malarial parasite, J. Biol. Chem., 274, 19383, 10.1074/jbc.274.27.19383

Peters, 1986, The chemotherapy of rodent malaria, Ann. Trop. Med. Parasitol., 80, 483, 10.1080/00034983.1986.11812054

Peters, 1999, The chemotherapy of rodent malaria., Ann. Trop. Med. Parasitol., 93, 325, 10.1080/00034983.1999.11813429

Posner, 2000, Carbon-centered radicals and rational design of new antimalarials, 289

Posner, 1994, Mechanism-based design, synthesis, and in vitro antimalarial testing of new 4-methylated trioxanes structurally related to artemisinin: the importance of a carbon-centered radical for antimalarial activity, J. Med. Chem., 37, 1256, 10.1021/jm00035a003

Posner, 1995, Further evidence supporting the importance of and the restrictions on a carbon-centered radical for high antimalarial activity of 1,2,4-trioxanes like artemisinin, J. Med. Chem., 38, 2273, 10.1021/jm00013a001

Price, 1999, Adverse effects in patients with acute falciparum malaria treated with artemisinin derivatives, Am. J. Trop. Med. Hyg., 60, 547, 10.4269/ajtmh.1999.60.547

Price, 1999, The pfmdr1 gene is associated with a multidrug-resistant phenotype in Plasmodium falciparum from the western border of Thailand, Antimicrob. Agents Chemother., 43, 2943, 10.1128/AAC.43.12.2943

Price, 1996, Effects of artemisinin derivatives on malaria transmissibility, Lancet, 347, 1654, 10.1016/S0140-6736(96)91488-9

Provot, 1999, Structure–activity relationships of synthetic tricyclic trioxanes related to artemisinin: the unexpected alkylative property of a 3-(methoxymethy) analog, Eur. J. Org. Chem., 8, 1935, 10.1002/(SICI)1099-0690(199908)1999:8<1935::AID-EJOC1935>3.0.CO;2-Y

Reed, 2000, Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparum, Nature, 403, 906, 10.1038/35002615

Robert, 1997, Characterization of the first covalent adduct between artemisinin and a heme model, J. Am. Chem. Soc., 119, 5968, 10.1021/ja970412g

Rosenthal, 1996, Hemoglobin catabolism and iron utilization by malaria parasites, Mol. Biochem. Parasitol., 83, 131, 10.1016/S0166-6851(96)02763-6

Sahr, 2001, Apparent drug failure following artesunate treatment of Plasmodium falciparum malaria in Freetown, Sierra Leone: four case reports, Ann. Trop. Med. Parasitol., 95, 445, 10.1080/00034980120072284

Schmuck, 2002, Neurotoxic mode of action of artemisinin, Antimicrob. Agents Chemother., 46, 821, 10.1128/AAC.46.3.821-827.2002

Scott, 1989, Qinghaosu-mediated oxidation in normal and abnormal erythrocytes, J. Lab. Clin. Med., 114, 401

Senok, 1997, Thalassaemia trait, red blood cell age and oxidant stress: effects on Plasmodium falciparum growth and sensitivity to artemisinin, Trans. R. Soc. Trop. Med. Hyg., 91, 585, 10.1016/S0035-9203(97)90037-7

Shukla, 1995, Molecular modeling studies of the artemisinin (qinghaosu)–hemin interaction: docking between the antimalarial agent and its putative receptor, J. Mol. Graph., 13, 215, 10.1016/0263-7855(94)00001-9

Skinner, 1996, In vitro stage-specific sensitivity of Plasmodium falciparum to quinine and artemisinin drugs, Int. J. Parasitol., 26, 519, 10.1016/0020-7519(96)89380-5

Targett, 2001, Artesunate reduces but does not prevent posttreatment transmission of Plasmodium falciparum to Anopheles gambiae, J. Infect. Dis., 183, 1254, 10.1086/319689

ter Kuile, 1993, Plasmodium falciparum: in vitro studies of the pharmacodynamic properties of drugs used for the treatment of severe malaria, Exp. Parasitol., 76, 85, 10.1006/expr.1993.1010

Utzinger, 2001, The potential of artemether for the control of schistosomiasis, Int. J. Parasitol., 31, 1549, 10.1016/S0020-7519(01)00297-1

van Vugt, 1998, Randomized comparison of artemether-benflumetol and artesunate-mefloquine in treatment of multidrug-resistant falciparum malaria, Antimicrob. Agents Chemother., 42, 135, 10.1128/AAC.42.1.135

van Vugt, 2000, Artemether–lumefantrine for the treatment of multidrug-resistant falciparum malaria, Trans. R. Soc. Trop. Med. Hyg., 94, 545, 10.1016/S0035-9203(00)90082-8

von Seidlein, 1998, A randomized controlled trial of artemether/benflumetol, a new antimalarial and pyrimethamine/sulfadoxine in the treatment of uncomplicated falciparum malaria in African children, Am. J. Trop. Med. Hyg., 58, 638, 10.4269/ajtmh.1998.58.638

Walker, 2000, Mechanisms of artemisinin resistance in the rodent malaria pathogen Plasmodium yoelii, Antimicrob. Agents Chemother., 44, 344, 10.1128/AAC.44.2.344-347.2000

Wei, 1994, Enhancement of hemin-induced membrane damage by artemisinin, Biochem. Pharmacol., 48, 737, 10.1016/0006-2952(94)90051-5

White, 1999, Antimalarial drug resistance and combination chemotherapy, Philos. Trans. R. Soc. Lond. B Biol. Sci., 354, 739, 10.1098/rstb.1999.0426

White, 1997, Assessment of the pharmacodynamic properties of antimalarial drugs in vivo, Antimicrob. Agents Chemother., 41, 1413, 10.1128/AAC.41.7.1413

Wittner, 1996, Atovaquone in the treatment of Babesia microti infections in hamsters, Am. J. Trop. Med. Hyg., 55, 219, 10.4269/ajtmh.1996.55.219

Wongsrichanalai, 1997, In vitro susceptibility of Plasmodium falciparum isolates in Vietnam to artemisinin derivatives and other antimalarials, Acta Trop., 63, 151, 10.1016/S0001-706X(96)00618-3

Wongsrichanalai, 1999, In vitro sensitivity of Plasmodium falciparum to artesunate in Thailand, Bull. World Health Organ., 77, 392

Woolfrey, 1998, Comparison of 3D quantitative structure–activity relationship methods: analysis of the in vitro antimalarial activity of 154 artemisinin analogues by hypothetical active-site lattice and comparative molecular field analysis, J. Comput. Aided Mol. Des., 12, 165, 10.1023/A:1007967517859

Wu, 1996, Ferrous ion induced cleavage of the peroxy bond in quinghaosu and its derivatives and the DNA damage associated with this process, Chem. Commun., 18, 2213, 10.1039/cc9960002213

Yang, 1993, Alkylation of human albumin by the antimalarial artemisinin, Biochem. Pharmacol., 46, 336, 10.1016/0006-2952(93)90425-V

Yang, 1994, Alkylation of proteins by artemisinin. Effects of heme, pH, and drug structure, Biochem. Pharmacol., 48, 569, 10.1016/0006-2952(94)90287-9

Zhang, 1992, Hemin-catalyzed decomposition of artemisinin (qinghaosu), Biochem. Pharmacol., 43, 1805, 10.1016/0006-2952(92)90713-S