Artemisinin and the Antimalarial Endoperoxides: from Herbal Remedy to Targeted Chemotherapy

Overview

Journal Microbiol Rev

Publisher American Society for Microbiology

Specialty Microbiology

Date 1996 Jun 1

PMID 8801435

Citations 144

Authors

S R Meshnick

T E Taylor

S Kamchonwongpaisan

Affiliations

Soon will be listed here.

Abstract

Artemisinin and its derivatives are endoperoxide-containing compounds which represent a promising new class of antimalarial drugs. In the presence of intraparasitic iron, these drugs are converted into free radicals and other electrophilic intermediates which then alkylate specific malaria target proteins. Combinations of available derivatives and other antimalarial agents show promise both as first-line agents and in the treatment of severe disease.

Citing Articles

Solidified reverse micellar solution-based chitosan-coated solid lipid nanoparticles as a new approach to enhance oral delivery of artemether in malaria treatment.

Kenechukwu F, Ugwu K, Offorbuike C, Ojukwu E, Gugu T, Eze R BMC Chem. 2025; 19(1):64.

PMID: 40057800 PMC: 11890727. DOI: 10.1186/s13065-025-01422-4.

Emerging trends and new developments in global research on artemisinin and its derivatives.

Lai Y, Zhang H, Chen X Heliyon. 2025; 11(1):e41086.

PMID: 39801992 PMC: 11720899. DOI: 10.1016/j.heliyon.2024.e41086.

Characterizing the pharmacological interaction of the antimalarial combination artefenomel-piperaquine in healthy volunteers with induced blood-stage Plasmodium falciparum to predict efficacy in patients with malaria.

Abd-Rahman A, Kaschek D, Kummel A, Webster R, Potter A, Odedra A BMC Med. 2024; 22(1):563.

PMID: 39609822 PMC: 11603672. DOI: 10.1186/s12916-024-03787-0.

Phosphorylation in the Proteome: A Meta-Analysis of Publicly Available Data Sets.

Camacho O, Ramsbottom K, Prakash A, Sun Z, Riverol Y, Bowler-Barnett E J Proteome Res. 2024; 23(12):5326-5341.

PMID: 39475123 PMC: 11629380. DOI: 10.1021/acs.jproteome.4c00418.

Evaluation of the binding interactions between Plasmodium falciparum Kelch-13 mutant recombinant proteins with artemisinin.

Md Yusuf N, Azman A, Abdul Aziz A, Ahmad Fuad F, Nasarudin R, Hisam S PLoS One. 2024; 19(8):e0306975.

PMID: 39146276 PMC: 11326563. DOI: 10.1371/journal.pone.0306975.

References

Mittelholzer M, Sorenson F, Haller L, Sturchler D . Efficacy of Ro 42-1611 (arteflene) in the treatment of patients with mild malaria: a clinical trial in Cameroon. Trop Med Parasitol. 1994; 45(3):288-91. View

Li G, Guo X, Jian H, Fu L, Shen L, Li R . Observation on the efficacy of qinghaosu suppository in 100 cases of falciparum malaria. J Tradit Chin Med. 1985; 5(3):159-61. View

Fry M, Beesley J . Mitochondria of mammalian Plasmodium spp. Parasitology. 1991; 102 Pt 1:17-26. DOI: 10.1017/s0031182000060297. View

Xiao S, Catto B . In vitro and in vivo studies of the effect of artemether on Schistosoma mansoni. Antimicrob Agents Chemother. 1989; 33(9):1557-62. PMC: 172702. DOI: 10.1128/AAC.33.9.1557. View

Acton N, Karle J, Miller R . Synthesis and antimalarial activity of some 9-substituted artemisinin derivatives. J Med Chem. 1993; 36(17):2552-7. DOI: 10.1021/jm00069a014. View

Melendez V, Peggins J, Brewer T, Theoharides A . Determination of the antimalarial arteether and its deethylated metabolite dihydroartemisinin in plasma by high-performance liquid chromatography with reductive electrochemical detection. J Pharm Sci. 1991; 80(2):132-8. DOI: 10.1002/jps.2600800209. View

Luo X, Shen C . The chemistry, pharmacology, and clinical applications of qinghaosu (artemisinin) and its derivatives. Med Res Rev. 1987; 7(1):29-52. DOI: 10.1002/med.2610070103. View

Lin A, Miller R . Antimalarial activity of new dihydroartemisinin derivatives. 6. alpha-Alkylbenzylic ethers. J Med Chem. 1995; 38(5):764-70. DOI: 10.1021/jm00005a004. View

Klayman D . Qinghaosu (artemisinin): an antimalarial drug from China. Science. 1985; 228(4703):1049-55. DOI: 10.1126/science.3887571. View

10.

Avery M, Gao F, Chong W, Mehrotra S, Milhous W . 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. 1993; 36(26):4264-75. DOI: 10.1021/jm00078a017. View

11.

Weatherall D . Common genetic disorders of the red cell and the 'malaria hypothesis'. Ann Trop Med Parasitol. 1987; 81(5):539-48. DOI: 10.1080/00034983.1987.11812155. View

12.

Merali S, Meshnick S . Susceptibility of Pneumocystis carinii to artemisinin in vitro. Antimicrob Agents Chemother. 1991; 35(6):1225-7. PMC: 284315. DOI: 10.1128/AAC.35.6.1225. View

13.

ELLIS D, Li Z, Gu H, Peters W, Robinson B, Tovey G . The chemotherapy of rodent malaria, XXXIX. Ultrastructural changes following treatment with artemisinine of Plasmodium berghei infection in mice, with observations of the localization of [3H]-dihydroartemisinine in P. falciparum in vitro. Ann Trop Med Parasitol. 1985; 79(4):367-74. View

14.

Woerdenbag H, Pras N, van Uden W, Wallaart T, Beekman A, Lugt C . Progress in the research of artemisinin-related antimalarials: an update. Pharm World Sci. 1994; 16(4):169-80. DOI: 10.1007/BF01872865. View

15.

Pe Than Myint , Shwe T, Soe L, Htut Y, Myint W . Clinical study of the treatment of cerebral malaria with artemether (qinghaosu derivative). Trans R Soc Trop Med Hyg. 1989; 83(1):72. DOI: 10.1016/0035-9203(89)90711-6. View

16.

Milhous W, Gerena L, Kyle D, Oduola A . In vitro strategies for circumventing antimalarial drug resistance. Prog Clin Biol Res. 1989; 313:61-72. View

17.

Wei N, Sadrzadeh S . Enhancement of hemin-induced membrane damage by artemisinin. Biochem Pharmacol. 1994; 48(4):737-41. DOI: 10.1016/0006-2952(94)90051-5. View

18.

Wernsdorfer W . Epidemiology of drug resistance in malaria. Acta Trop. 1994; 56(2-3):143-56. DOI: 10.1016/0001-706x(94)90060-4. View

19.

Gu H, Warhurst D, Peters W . Uptake of [3H] dihydroartemisinine by erythrocytes infected with Plasmodium falciparum in vitro. Trans R Soc Trop Med Hyg. 1984; 78(2):265-70. DOI: 10.1016/0035-9203(84)90296-7. View

20.

Kumar N, Zheng H . Stage-specific gametocytocidal effect in vitro of the antimalaria drug qinghaosu on Plasmodium falciparum. Parasitol Res. 1990; 76(3):214-8. DOI: 10.1007/BF00930817. View