Qinghaosu (artemisinin): Chemistry and pharmacology

Acta Pharmacologica Sinica

Volumn 33, Issue 9, 2012, Pages 1141-1146

  Li, Ying ^a  

^a SHANGHAI INSTITUTE OF MATERIA MEDICA   (China)

Author keywords

anticancer activity; antimalarial activity; artemisinin; immunosuppressive activity; mode of action; Qinghaosu; structure modification

Indexed keywords

ARTEMISININ; ARTESUNATE; CHLOROQUINE; DIHYDROARTEMISININ; FERROUS ION; FREE RADICAL; PEROXIDE; TETRAHYDROFURAN;

ANTIMALARIAL ACTIVITY; CHINA; CLINICAL TRIAL (TOPIC); DRUG EFFICACY; DRUG SCREENING; DRUG SOLUBILITY; DRUG STABILITY; FRIEDEL CRAFTS REACTION; HUMAN; LUPUS ERYTHEMATOSUS; NONHUMAN; PLASMODIUM FALCIPARUM; REVIEW; STRUCTURE ACTIVITY RELATION;

ANIMALS; ANTIMALARIALS; ANTINEOPLASTIC AGENTS; ARTEMISININS; CHINA; DRUG DESIGN; HUMANS; MEDICINE, CHINESE TRADITIONAL; RESEARCH;

EID: 84865988767     PISSN: 16714083     EISSN: 17457254     Source Type: Journal    
DOI: 10.1038/aps.2012.104     Document Type: Review

References (69)

1. Zhang JF. A detailed chronological record of project 523 and the discovery and development of Qinghaosu (Artemisinin). Guangzhou: Yangcheng Evening News Publisher; 2006. Chinese.
2. Li Y, Wu YL. A golden phoenix arising from the herbal net - A review and reflection on the study of antimalarial drug qinghaosu. Front Chem China 2010; 5: 357-422.
3. Liu JM, Ni MY, Fan JF, Tu YY, Wu ZH, Wu YL, et al. Structure and reactions of arteannuin. Acta Chim Sin 1979; 37: 129-43. Chinese.
4. Li Y, Yu PL, Chen YX, Li LQ, Gai YZ, Wang DS, et al. Synthesis of some derivatives of artemisinin. Ke Xue Tong Bao 1979; 24: 667-9. Chinese.
5. Li Y, Yu PL, Chen YX, Li LQ, Gai YZ, Wang DS, et al. Studies on analogs of artemisinin I. The synthesis of ethers, carboxylic esters and carbonates of dihydroartemisinine. Yao Xue Xue Bao 1981; 16: 429-39. Chinese.
6. Gu HM, Lu BF, Qu ZX. Antimalarial activities of 25 derivatives of artemisinine against chloroquine-resistant Plasmodium berghei. Acta Pharmacol Sin 1980; 1: 48-50. Chinese. (Pubitemid 11175605)
7. Liu X. Study on artemisinin derivatives. Yao Xue Tong Bao 1980; 15: 183. Chinese.
8. Meshnick SR, Tsang TW, Lin FB, Pan HZ, Chang CN, Kuypers F, et al. Activated oxygen mediates the antimalarial activity of qinghaosu. Prog Clin Biol Res 1989; 313: 95-104.
9. Meshnick SR, Tomas A, Ranz A, Xu CM, Pan HZ. Artemisinin (qinghaosu): the role of intracellular hemin in its mechanism of antimalarial action. Mol Biochem Parasitol 1991; 49: 181-9.
10. Posner GH, Oh CH. A regiospecifically oxygen-18 labeled 1,2,4-trioxane: a simple chemical mode system to probe the mechanism(s) for the antimalarial activity of artemisinin (qinghaosu). J Am Chem Soc 1992; 114: 8328-9.
11. Jefford CW. Why artemisinin and certain synthetic peroxides are potent antimalarials. Implications for the mode of action. Curr Med Chem 2001; 8: 1803-26. (Pubitemid 33134072)
12. Olliaro PL, Haynes RK, Meunier B, Yuthavong Y. Possible modes of action of the artemisinin-type compounds. Trends Parasitol 2001; 17: 122-6. (Pubitemid 32422178)
13. Posner GH, O'Neill PM. Knowledge of the proposed chemical mechanism of action and cytochrome P 450 metabolism of antimalarial trioxanes like artemisinin allows rational design of new antimalarial peroxides. Acc Chem Res 2004; 37: 394-404.
14. O'Neill PM, Barton VE, Ward SA. The molecular mechanism of action of artemisinin - the debate continues. Molecules 2010; 15: 1705-21.
15. Qinghaosu antimaraia coordinating research group: Antimararia studies on qinghaosu. Chin Med J 1979; 92: 811-6.
16. Antimararial efficacy and mode of action of qinghaosu and its derivatives in experimental models. China Cooperative Research Group on qinghaosu and its derivatives as antimalarials. J Tradit Chin Med 1982; 2: 17-24.
17. Jin YG, Teng XH, Sun CP. Free radicals and mechanism of toxicity of sodium artesunate. Chin J Pharmacol Toxicol 1989; 2: 60-5. Chinese.
18. Wang JY, Yuan LZ, Wang MD. Inhibition of sodium artesunate on rat erythrocyte membrane Na+-K+-exchanging ATPase in vitro. Yao Xue Xue Bao 1995; 16: 524-6. Chinese.
19. Shi XC, Zhang QL, Wu K, Wang S, Sun CP, Wang ZQ. Hemopoietotoxicity in pregnant mice and their embryos induced by free radicals derived from sodium artesunate. Chin J Pharmacol Toxicol 1997; 11: 226-8. Chinese. (Pubitemid 27365946)
20. Chen Y, Zhu SM, Chen HY, Li Y. Artesunate interaction with heme. Bioelectrochem Bioenerg 1988; 44: 295-300.
21. Cheng F, Shen JH, Luo XM, Zhu WL, Gu JD, JI RY, et al. Molecular docking and 3-D-QSAR studies on the possible antimalarial mechanism of artemisinin analogues. Bioorg Med Chem 2002; 10: 2883-91. (Pubitemid 34761866)
22. Wu WM, Yao ZJ, Wu YL, Jiang K, Wang YF, Chen HB, et al. Ferrous ion induced cleavage of the peroxy bond in qinghaosu and its derivatives and the DNA damage associated with this process. Chem Commun 1996; 18: 2213-4. (Pubitemid 26329275)
23. Wu WM, Wu YK, Wu YL, Yao ZJ, Zhou CM, Li Y, et al. A unified mechanism framework for the Fe(II)-induced cleavage of qinghaosu and derivatives/analogs. The first spin-trapping evidence for the earlier postulated secondary C-4 radical. J Am Chem Soc 1998; 120: 3316-25. (Pubitemid 28289067)
24. Butler AR, Gilbert BC, Hulme P, Irvine LR, Renton L, Whitwood AC. 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 Rad Res 1998; 28: 471-6. (Pubitemid 28395810)
25. Zhu DY, Huang BS, Chen ZL, Yin ML, Yang YM, Dai ML, et al. Isolation and identification of the metabolite of artemisinin in human. Yao Xue Xue Bao 1983; 4: 194-7. Chinese. (Pubitemid 14229417)
26. Lee IS, Hufford CD. Metabolism of antimalarial sesquiterpene lactones. Pharmacol Ther 1990; 48: 345-55.
27. Wang DY, Wu YL, Wu YK, Liang J, Li Y. Further evidence for the participation of primary carbon-centered free-radicals in the antimalarial action of the the qinghaosu (artemisinin) series of compounds. ChemInform 2001; 32: 605-9.
28. Wang DY, Wu YK, Wu YL, Li Y, Shan F. Synthesis, iron(II)-induced cleavage and in vivo antimalarial efficacy of 10-(2-hydroxy-1-naphthyl)-dexoxqinghaosu (-deoxoartemisinin). J Chem Soc Perkin Trans 1. 1999; 1827-31.
29. Wang J, Huang L, Li J, Fan Q, Long Y, Li Y, et al. Artemisinin directly targets malaria mitochondria through its specific mitochondrial activation. PLoS One 2010; 5: e9582.
30. Wu YL, Chen HB, Jiang K, Li Y, Shan F, Wang DY, et al. Interaction of biomolecules with qinghaosu (artemisinin) and its derivatives in the presence of ferrous ion- an exploration of antimalarial mechanism. Pure Appl Chem 1999; 71: 1139-42.
31. Wang DY, Wu YL. 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. Chem Commun 2000; 22: 2193-4.
32. Wu YK, Yue ZY, Wu YL. Interaction of qinghaosu (artemisinin) with cysteine sulfhydryl mediated by traces of non-heme iron. Angew Chem Int Ed 1999; 38: 2580-2.
33. Wu WM, Chen YL, Zhai ZL, Xiao SH, Wu YL. Study on the mechanism of action of artemether against schistosomes - The identification of cysteine adducts of both carbon-centered free-radicals derived from artemether. Bioorg Med Chem Lett 2003; 13: 1645-7.
34. Chen DJ, Fu LF, Shao PP, Wu FZ, Fan CZ, Shu Y, et al. The experimental studies of artemisinin against Schistosoma japonicum in animals. Zhonghua Yi Xue Za Zhi 1980; 60: 422-5. Chinese.
35. Le WJ, Wang GF, You JQ, Xie RR, Mei JY. The experimental studies of artemisinin derivatives against Schistosoma japonicum in animals. Yao Xue Tong Bao 1980; 15: 182. Chinese.
36. Xiao SH, Tanner M, N'Goran EK, Utzinger J, Chollet J, Bergquist R, et al. Recent investigations of artemether, a novel agent for the prevention of Schistosomiasis japonica, mansoni and haematobia. Acta Trop 2002; 82: 175-81. (Pubitemid 34518567)
37. Sun WC, Han JX, Yang WY, Deng DA, Yue XF. Antitumor activities of 4. derivatives of artemisinic acid and artemisinin B, in vitro. Acta Pharmacol Sin 1992; 13: 541-3. Chinese.
38. Deng DA, Xu CH, Cai JC. Derivatives of arteannuin B with antileukemia activity. Yao Xue Xue Bao 1992; 27: 317-20. Chinese.
39. Efferth T, Dunstan H, Sauerbrey A, Miyachi H, Chitambar CR. The antimalarial artesunate is also active ahainst cancer. Int J Oncol 2001; 18: 767-73.
40. Crespo-Ortiz MP, Wei MQ. Antitumor activity of artemisinin and its derivatives: from a well-known antimalarial agent to a potential anticancer drug. J Biomed Biotech 2012; 2012: 247597.
41. Li Y, Shan F, Wu JM, Wu GS, Ding J, Xiao D, et al. Novel antitumor artemisinin derivatives targeting G1 phase of the cell cycle. Bioorg Med Chem Lett 2001; 11: 5-8. (Pubitemid 32006112)
42. Wu JM, Shan F, Wu GS, Li Y, Ding J, Xiao D, et al. Synthesis and cytotoxicity of artemisinin derivatives containing cyanoarylmethyl group. Eur J Med Chem 2001; 36: 240-5
43. Efforth T. Willmar Schwabe Award 2006: Antiplasmodial and antitumor activity of artemisinin from bench to bedside. Planta Med 2007; 73: 299-309.
44. Liu Y, Lok CN, Ko BCB, Shum TYT, Wong MK, Che CM. Subcellular localization of a fluorescent artemisinin derivative to endoplasmic reticulum. Org Lett 2010; 12: 1420-3.
45. Morrissey C, Gallis B, Solazzi JW, Kim BJ, Gulati R, Vakar-Lopez F, et al. Effect of artemisinin derivatives on apoptosis and cell cycle in prostate cancer cells. Anticancer Drug 2010; 21: 423-32.
46. Lu JJ, Meng LH, Cai YJ, Chen Q, Tong LJ, Lin LP, et al. Dihydroartemisinin induces apoptosis in HL-60 leukemia cells dependent of iron and p38 mitogen-activated protein kinase activation but independent of reactive oxygen species. Cancer Biol Ther 2008; 7: 1017-23.
47. Lu JJ, Meng LH, Shankavaram UT, Zhua CH, Tong LJ, Chen G, et al. Dihydroartemisinin accelerates c-MYC oncoprotein degradation and induces apoptosis in c-MYC-overexpressing tumor cells. Biochem Pharmacol 2010; 80: 22-30.
48. Lu JJ, Chen SM, Zhang XW, Ding J, Meng LH. The anti-cancer activity of dihydroartemisinin is associated with induction of iron-dependent endoplasmic reticulum stress in colorectal carcinoma HCT116 cells. Invest New Drugs 2011; 29: 1276-83.
49. Lu JJ, Chen SM, Ding J, Meng LH. Characterization of dihydroartemisinin- resistant colon carcinoma HCT116/R cell line. Mol Cell Biochem 2012; 360: 329-37.
50. Yu QB, Gao YX. 56 cases of lupus erythematosus treated with artesunate. Zhonghua Pi Fu Ke Za Zhi 1997, 30: 51-2. Chinese.
51. Yang ZS, Zhou WL, Sui Y, Wang JX, Wu JM, Zhou Y, et al. Synthesis and immunosuppressive activity of new artemisinin derivatives. Part I. [12 (? or ?)-Dihydroartemisininoxy] phen(ox)yl aliphatic acids/esters. J Med Chem 2005; 48: 4608-17. (Pubitemid 40993421)
52. Yang ZS, Wang JX, Zhou Y, Zuo JP, Li Y. Synthesis and immunosuppressive activity of new artemisinin derivatives. Part 2: 2-[12(? or ?)-Dihydro- artemisininoxymethyl-(or 1?-ethyl) phenoxyl propionic acids and esters. Bioorg Med Chem 2006; 14: 8043-9. (Pubitemid 44739994)
53. Zhang JX, Wang JX, Zhang Y, Zuo JP, Wu JM, Sui Y, et al. Synthesis and immunosuppressive activity of new artemisinin derivatives containing polyethylene glycol group. Yao Xue Xue Bao 2006; 41: 65-70. Chinese. (Pubitemid 43350973)
54. Li Y, Zhu YM, Jiang HJ, Pan JP, Wu GS, Wu JM, et al. Synthesis and antimalarial activity of artemisinin derivatives containing an amino group. J Med Chem 2000; 43: 1635-40. (Pubitemid 30238446)
55. Zhou WL, Wu JM, Wu QL, Wang JX, Zhou Y, Zhou R, et al. A novel artemisinin derivative, 3-(12-beta-artemisininoxy) phenoxyl succinic acid (SM735), mediates immunosuppressive effects in vitro and in vivo. Acta Pharmacol Sin 2005; 26: 1352-8. (Pubitemid 41607008)
56. Wang JX, Tang W, Shi LP, Wan J, Zhou R, Ni J, et al. Investigation of the immunosuppressive activity of artemether on T cell activation and proliferation. Br J Pharmacol 2007; 150: 652-61. (Pubitemid 46355561)
57. Wang Z, Qiu J, Guo TB, Liu A, Wang Y, Li Y, et al. Anti-inflammatory properties and regulatory mechanism of a novel derivative of artemisinin in experimental autoimmune encephalomyelitis. J Immunol 2007; 179: 5958-65.
58. Wang JX, Tang W, Shi LP, Wan J, Zhou R, Ni J, et al. Investigation of the immunosuppressive activity of artemether on T-cell activation and proliferation. Br J Pharmacol 2007; 150: 652-61. (Pubitemid 46355561)
59. Wang JX, Tang W, Yang ZS, Wan J, Shi LP, Zhang Y, et al. Suppressive effect of a novel water-soluble artemisinin derivative SM 905 on T cell activation and proliferation in vitro and in vivo. Eur J Pharmacol 2007; 564: 211-8. (Pubitemid 46957514)
60. Wang JX, Tang W, Zhou R, Wan J, Shi LP, Zhang Y, et al. The new water-soluble artemisinin derivative SM 905 ameliorates collagen induced arthritis by suppression of inflammatory and Th17 responses. Br J Pharmacol 2008, 153: 1303-10. (Pubitemid 351415509)
61. Wang JX, Hou LF, Yang Y, Tang W, Li Y, Zuo JP. SM 905, a novel artemisinin derivative, inhibition of NO and pro-inflammatory cytokine production by suppressing MAPK and NF-kappa B pathways in RAW 264.7 macrophages. Acta Pharmacol Sin 2009; 30: 1428-35.
62. Hou LF, He SJ, Wang JX, Yang Y, Zhu FH, Zhou Y, et al. SM 934, a water-soluble derivative of artemisinin, exerts immunosuppressive functions in vitro and in vivo. Int Immunopharmacol 2009; 9: 1509-17.
63. Hou LF, He SJ, Li X, Yang Y, He PL, Zhou Y, et al. Oral administration of artemisinin analog SM934 ameliorates lupus syndromes in MRL/ lpr mice by inhibiting Th1 and Th17 cell responses. Arthritis Rheum 2011; 63: 2445-55.
64. Hou LF, He SJ, Li X, Wan CP, Yang Y, Zhang XH, et al. SM934 treated lupus-prone NZB×NZW F1 mice by enhancing macrophage interleukin-10 production and suppressing pathogenic T cell development. PLoS One 2012; 7: e32424.
65. Li Y, Zhu Y, Zhang Y, Zhou JY, Cai L, Xie SW, inventors; Qinghaosu dimer containing nitrogen atom(s), its preparation and use. Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Shanghai Institute of Planned Parenthood Research. Chinese Patent 201110034154.9, 2011 Jan 31.
66. Mi JQ, Li Y, Liu JJ, Zhang Y, Cai X, Wang ZY, inventors; Use of a qinghaosu dimer. Ruijin Hospital, Shanghai Jiao Tong University School of Medicine and Shanghai Institute of Materia Medica, Chinese Academy of Sciences. Chinese Patent 201110034201.X, 2011 Jan 31.
67. Mi JQ, Li Y, Ni RM, Zhang Y, Wang J, Cai X, Wang ZY, inventors; Qinghaosu derivative and its salt, a new type of agent for treatment of acute leukemia. Ruijin Hospital, Shanghai Jiao Tong University School of Medicine and Shanghai Institute of Materia Medica, Chinese Academy of Sciences. Chinese Patent 201210011774.5, 2012 Jan 16.
68. Mi JQ, Li Y, Ni RM, Zhang Y, Wang J, Cai X, Wang ZY, inventors; Qinghaosu derivative and its salt, a new type of agent for treatment of leukemia. Ruijin Hospital, Shanghai Jiao Tong University School of Medicine and Shanghai Institute of Materia Medica, Chinese Academy of Sciences. Chinese Patent 201210012386.9, 2012 Jan 16.
69. Mi JQ, Li Y, Peng Y, Zhang Y, Wang J, Cai X, Wang ZY, inventors; Qinghaosu derivative and its salt, a new type of agent for treatment of acute myelocytie leukemia. Ruijin Hospital, Shanghai Jiao Tong University School of Medicine and Shanghai Institute of Materia Medica, Chinese Academy of Sciences. Chinese Patent 201210012204.8, 2012 Jan 16.