Chloroquine - Some open questions on its antimalarial mode of action and resistance

Drug Resistance Updates

Volumn 2, Issue 3, 1999, Pages 180-187

  Ginsburg, Hagai ^a   Krugliak, Miriam ^a  

^a HEBREW UNIVERSITY OF JERUSALEM   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

CATION; CHLOROQUINE; GLUTATHIONE; HEMATIN; HEMOGLOBIN; HEMOZOIN; MUTANT PROTEIN;

ANTIMALARIAL ACTIVITY; CELL VACUOLE; DETOXIFICATION; DRUG MECHANISM; DRUG RESISTANCE; HOST CELL; HUMAN; MEMBRANE PERMEABILITY; NONHUMAN; PH; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN POLYMERIZATION; REVIEW;

EID: 0033150368     PISSN: 13687646     EISSN: None     Source Type: Journal    
DOI: 10.1054/drup.1999.0085     Document Type: Article

References (84)

1. Ginsburg H, Krugliak M. Quinoline-containing antimalarials - Mode of action, drug resistance and its reversal - An update with unresolved puzzles. Biochem Pharmacol 1992;43:63-70.
2. Slater AF. Chloroquine - Mechanism of drug action and resistance in plasmodium falciparum. Pharmacol Ther 1993; 57: 203-235.
3. Foote SJ, Cowman AF.The mode of action and the mechanism of resistance to antimalarial drugs.Actatrop 1994;56: 157-171.
4. Cowman AF. Mechanisms of drug resistance in malaria. Aust NZ J Med 1995; 25: 837-844.
5. Ward SA, Bray PG, MUngthin M, Hawley SR. Current views on the mechanisms of resistance to quinoline- Containing drugs in plasmodium falciparum. Ann Trop Med Parasitol 1995; 89: 121-124.
6. Cowman AF.The mechanisms of drug action and resistance in malaria. Molecular Genetics of Drug Resistance 1997; 3: 221-246.
7. Ward SA, Bray PG, Hawley SR. Quinoline resistance mechanisms in plasmodium falciparum: The debate goes on. Parasitology 1997; 114: S125-S136.
8. Foley M,Tilley L. Quinoline antimalarials: Mechanisms of action and resistance. Int J Parasitol 1997; 27: 231-240.
9. Bray PG, MUngthin M, Ridley RG,Ward SA.Access to hematin:the basis of chloroquine resistance. Mol Pharmacol 1998; 54: 170-179.
10. Foley M,Tilley L. Quinoline antimalarials: Mechanisms of action and resistance and prospects for new agents. Pharmacol Ther 1998; 79: 55-87.
11. Chou AC, Fitch CD. Mechanism of hemolysis induced by ferriprotoporphyrin IX. J Clin Invest 1981; 68: 672-677.
12. Chou A, Fitch C. Hemolysis of mouse erythrocytes by ferriprotoporphyrin IX and chloroquine chemotherapeutic implications. J Clin Invest 1980; 66:856-858.
13. Fitch CD, Chevli R, Banyal HS et al. Lysis of plasmodium falciparum by ferriprotoporphyrin IX and a chloroquine- Ferriprotoporphyrin IX complex.Antimicrobagents Chemother 1982; 21:819-822.
14. SlAter A, SWiggard W, Orton B et al. An iron-carboxylate bond links the heme units of malaria pigment. Proc Natl Acad Sci USA 1991; 88: 325-329.
15. Atamna H, Ginsburg H. Heme degradation in the presence of glutathione - A proposed mechanism to account for the high levels of non- Heme iron found in the membranes of hemoglobinopathic red blood cells. J Biol Chem. 1995; 270: 24876-24883.
16. Ginsburg H, Famin O, Zhang JM et al. Inhibition of glutathione-dependent degradation of heme by chloroquine and amodiaquine as a possible basis for their antimalarial mode of action. Biochem Pharmacol 1998; 56: 1305-1313.
17. Blauer G,Akkawi M. Investigations of B- And β-hematin. J Inorg Biochem 1997; 66: 145-152.
18. Dorn A,Vippagunta SR, Matile H et al.An assessment of drug-haematin binding as a mechanism for inhibition of haematin polymerisation by quinoline antimalarials. Biochem Pharmacol 1998; 55: 727-736.
19. Chou AC, Fitch CD. Control of heme polymerase by chloroquine and other quinoline derivatives. Biochem Biophys Res Commun 1993; 195: 422-427.
20. Zhang J, Krugliak M, Ginsburg H.The fate of ferriprotoporphyrin IX in malaria infected erythrocytes in conjunction with the mode of action of antimalarial drugs. Mol Biochem Parasitol 1999; 99: 129-141.
21. Chou A, Chevli R, Fitch C. Ferriprotoporphyrin IX fulfills the criteria for identification as the chloroquine receptor of malaria parasites. Biochemistry. 1980; 19: 1543-1549.
22. Vander Jagt DL, Hunsaker LA, Campos NM. Characterization of a hemoglobin-degrading, low molecular weight protease from plasmodium falciparum. Mol Biochem Parasitol 1986; 18: 389-400.
23. MUngthin M, Bray PG, Ridley RG,Ward SA. Central role of hemoglobin degradation in mechanisms of action of 4-aminoquinolines, quinoline methanols, and phenanthrene methanols.Antimicrob Agents Chemother 1998; 42: 2973-2977.
24. Krugliak M, Ginsburg H. Studies on the antimalarial mode of action of quinoline-containing drugs -time-dependence and irreversibility of drug action, and interactions with compounds that alter the function of the parasite's food vacuole. Life Sci 1991; 49: 1213-1219.
25. 3h] chloroquine by drug-sensitive and -resistant strains of the human malarial parasite plasmodium falciparum. Biochem Pharmacol 1986; 35:3805-3812.
26. LightWRI, Olson JS.Transmembrane movement of heme.J Biol Chem 1990; 265: 15623-15631.
27. LightWRI, Olson JS.The effect of lipid composition on the rate and extent of heme binding to membranes.J Biol Chem 1990; 26: 15632-15637.
28. Ginsburg H, Demel RA.The effect of protoporphyrin IX and chloroquine on phospholipid monolayer and the possible implications to antimalarial activity. Biochim Biophys Acta 1983; 732: 316-319.
29. Wood PA, Eaton JW. Hemoglobin catabolism and host-parasite heme balance in chloroquine-sensitive and chloroquine-resistant plasmodium berghei infections. Am J Trop Med Hyg 1993; 48: 465-472.
30. Lee P,Ye Z,Van DyKe K, Kirk RG.X-ray microanalysis of plasmodium falciparum and infected red blood cells: Effect of qinghaosu and chloroquine on potassium, sodium, and phosphorus composition.Am J Trop Med Hyg 1988; 39: 157-165.
31. Ribeiro MCD,AugustO O, Ferreira AMD. Influence of quinoline-containing antimalarials in the catalase activity of ferriprotoporphyrin IX.J Inorg Biochem 1997; 65: 15-23.
32. Ribeiro MCD,AugustO O, Ferreira AMD. Inhibitory effect of chloroquine and the peroxidase activity of ferriprotoporphyrin IX. J Chem Soc Dalton Trans 1995; 3759-3766.
33. Loria P, Miller S, Foley M,Tilley L. Inhibition of the peroxidative degradation of haem as the basis of action of chloroquine and other quinoline antimalarials. Biochem J 1999; 339: 363-370.
34. Atamna H, Ginsburg H. Origin of reactive oxygen species in erythrocytes infected with plasmodium falciparum. Mol Biochem Parasitol 1993; 61: 231-241.
35. Malhotra K, Salmon D, Le B,Vilde J-L. Potentiation of chloroquine activity against plasmodium falciparum by the peroxidase-hydrogen peroxide system.Antimicrob Agents Chemother 1990; 34: 1981-1985.
36. Martin S, OduolA A, Milhous W. Reversal of chloroquine resistance in plasmodium falciparum by verapamil. Science 1987; 235:899-901.
37. Bitonti AJ, SjoerdsmA A, McCann PP et al. Reversal of chloroquine resistance in malaria parasite plasmodium falciparum by desipramine. Science 1988; 242: 1301-1303.
38. Bray PG,Ward SA.A comparison of the phenomenology and genetics of multidrug resistance in cancer cells and quinoline resistance in plasmodium falciparum. Pharmacol Ther 1998; 77: 1-28.
39. Foote SJ,Thompson JK, Cowman AF, Kemp DJ.Amplification of the multidrug resistance gene in some chloroquine-resistant isolates of P. Falciparum. Cell 1989; 57:921 -930.
40. Zalis MG,Wilson CM, Zhang Y,Wirth DF. Characterization of the pfmdr2 gene for plasmodium falciparum. Mol Biochem Parasitol 1993; 62: 83-92.
41. Cowman AF, Karcz S, Galatis D, Culvenor JG.A p-glycoprotein homologue of plasmodium falciparum is localized on the digestive vacuole. J Cell Biol 1991; 113: 1033-1042.
42. Karcz SR, Galatis D, Cowman AF. Nucleotide binding properties of a p-glycoprotein homologue from plasmodium falciparum. Mol Biochem Parasitol 1993; 58: 269-276.
43. KrogstaD D, Gluzman I, Kyle D et al. Efflux of chloroquine from plasmodium falciparum: Mechanism of chloroquine resistance. Science 1987; 238: 1283-5.
44. Volkman SK, Cowman AF,Wirth DF. Functional complementation of the ste6 gene of saccharomyces cerevisiae with the pfmdr I gene of plasmodium falciparum. Proc Natl Acad Sci USA 1995; 92: 8921-9825.
45. Ruetz S, Delling U, Brault M, Schurr E, Gros P:The pfmdr I gene of plasmodium falciparum confers cellular resistance to antimalarial drugs in yeast cells (vol 93, pg 9942, 1996). Proc Nat Acad Sci USA 1999; 96: 1810.
46. Wilson CM,Volkman SK,Thaithong S et al.Amplification of pfmdr I associated with mefloquine and halofantrine resistance in plasmodium falciparum from thailand. Mol Biochem Parasitol 1993; 57: 151-160.
47. Barnes DA, Foote SJ, Galatis D, Kemp DJ, Cowman AF. Selection for high-level chloroquine resistance results in deamplification of the pfmdr I gene and increased sensitivity to mefloquine in plasmodium falciparum. EMBO J 1992; 11: 3067-3075.
48. Foley M, Deady LW, Ng K, Cowman AF,Tilley L. Photoaffinity labeling of chloroquine-binding proteins in plasmodium falciparum.J Biol Chem 1994; 269: 6955-6961.
49. Wellems TE, Panton LJ, Gluzman IY et al. Chloroquine resistance not linked to mdr-like genes in a plasmodium falciparum cross. Nature 1990; 345: 253-5.
50. Foote SK, Kyle DJ, Martin RK et al. Several alleles of the multidrug-resistance gene are closely linked to chloroquine resistance in plasmodium falciparum. Nature 1990; 345: 255-257.
51. Basco LK, Lebras J, Rhoades Z,Wilson CM.Analysis of pfmdr I and drug susceptibility in fresh isolates of plasmodium falciparum from subsaharan africa. Mol Biochem Parasitol 1995; 74: 157-166.
52. Cox-Singh J, Singh B, AliAs A,Abdullah MS.Assessment of the association between three pfmdr I point mutations and chloroquine resistance in vitro of malaysian plasmodium falciparum isolates.Trans R Soc Trop Med Hyg 1995; 89: 436-437.
53. Adagu IS, Dias F, Pinheiro L et al. Guinea bissau:association of chloroquine resistance of plasmodium falciparum with the tyr86 allele of the multiple drug-resistance gene pfmdr I .Trans R Soc Trop Med Hyg 1996; 90: 90-91.
54. Durasingh MT, Drakeley CJ, Muller O et al. Evidence for selection for the tyrosine-86 allele of the pfmdr I gene of plasmodium falciparum by choloroquine and amodiaquine. Parasitology 1997; 114: 205-211.
55. (tyr) polymorphism in lambarene, gabon. Parasitology 1998; 116: 211-217.
56. Basco LK, Ringwald P. Molecular epidemiology of malaria in yaounde, cameroon. Iii.analysis of chloroquine resistance and point mutations in the multidrug resistance I (pfmdr I) gene of plasmodium falciparum.Am J Trop Med Hyg 1998; 59: 577-581.
57. Basco LK, DePEcoulas PE, Lebras J,Wilson CM. Plasmodium falciparum: Molecular characterization of multidrug - Resistant cambodian isolates. Exp Parasitol 1996; 82: 97-103.
58. Awad el Kariem FM, Miles MA,Warhurst DC. Chloroquine-resistant plasmodium falciparum isolates from the sudan lack 2 mutations in the pfmdr I gene thought to be associated with chloroquine resistance.Trans R Soc Trop Med Hyg 1992; 86: 587-589.
59. HaruKi K, Bray PG,Ward SA, HoMMel M, Ritchie GY. Chloroquine resistance of plasmodium falciparum: Further evidence for a lack of association with mutations of the pfmdr I gene.Trans R Soc Trop Med Hyg 1994; 88: 694.
60. Bhattacharya PR, BiSwaS S, Kabilan L.Alleles of the plasmodium falciparum pfmdr I gene appear not to be associated with chloroquine resistance in india.Trans R Soctrop Med Hyg 1997; 91: 454-455.
61. Von SeidLein L, Duraisingh MT, Drakeley CJ et al. Polymorphism of the pfmdr I gene and chloroquine resistance in plasmodium falciparum in the gambia.Trans R Soc Trop Med Hyg 1997; 91:450-453.
62. (tyr) polymorphisms, thought to be associated with chloroquine resistance, are present in chloroquine-resistant and -sensitive brazilian field isolates of plasmodium falciparum. Exp Parasitol 1998; 88: 64-68.
63. Slater AF, Cerami A. Inhibition by chloroquine of a novel haem polymerase enzyme activity in malaria trophozoites. Nature 1992; 355: 167-169.
64. Goldberg DE, Slater AFG, Beavis R et al. Hemoglobin degradation in the human malaria pathogen plasmodium falciparum - A catabolic pathway initiated by a specific aspartic protease. J Exp Med 1991; 173:961-969.
65. van Es HHG, Renkema H,Aerts H, Schurr E. Enhanced lysosomal acidification leads to increased chloroquine accumulation in CHO cells expressing the pfmdr I gene. Mol Biochem Parasitol 1994; 68: 209-219.
66. Riordan JR.The cystic fibrosis transmembrane conductance regulator.Annu Rev Physiol 1993; 55: 609-630.
67. Rubio JP, Cowman AF.The atp-binding cassette (ABC) gene family of plasmodium falciparum. Parasitol Today 1996; 12: 135-140.
68. Lukacs GL, Chang XB, KartNer N et al.The cystic fibrosis transmembrane regulator is present and functional in endosomes - Role as a determinant of endosomal ph. J Biol Chem 1992; 267: 14568-14572.
69. GearyTG, Divo AA,Jensen JB, Zangwill M, Ginsburg H. Kinetic modelling of the response of plasmodium falciparum to chloroquine and its experimental testing in vitro. Implications for Mechanism of Action and of Resistance to The Drug. Biochem Pharmacol 1990; 40: 685-691.
70. Ginsburg H, Stein WD. Kinetic modelling of chloroquine uptake by malaria-infected erythrocytes - Assessment of the factors that may determine drug resistance. Biochem Pharmacol 1991; 41: 1463-1470.
71. Saliba KJ, Folb PI, Smith PJ. Role for the plasmodium falciparum digestive vacuole in chloroquine resistance. Biochem Pharmacol 1998; 56: 313-320.
72. KUnzelmann K, Slotki IN, Koslowsky T et al. Effects of p-glycoprotein expression on cyclic AMP and volume-activated ion fluxes and conductances in HT-29 colon adenocarcinoma cells.J Cell Physiol 1998; 161: 393-406.
73. van Es HHG, Karcz S, Chu F et al. Expression of the plasmodial pfmdr I gene in mammalian cells is associated with increased susceptibility to chloroquine. Mol Cell Biol 1994; 14: 2419-2428.
74. Dubois VL, Platel DFN, Pauly G,Tribouley-Duret J. Plasmodium berghei: Implication of intracellular glutathione and its related enzyme in chloroquine resistance in vivo. Exp Parasitol 1995; 81: 117-124.
75. Su XZ, Kirkman LA, Fujioka H,Wellems TE: complex polymorphisms in an similar to 330 kda protein are linked to chloroquine-resistant p-falciparum in southeast asia and africa. Cell 1997; 91: 593-603.
76. Bray PG, Boulter MK, Ritchie GY, Howells RE,Ward SA. Relationship of global chloroquine transport and reversal of resistance in plasmodium falciparum. Mol Biochem Parasitol 1994; 63: 87-94.
77. Slomianny C, Prensier G.A cytochemical ultrastructural study of the lysosomal system of different species of malaria parasites.J Protozool. 1990; 37:465-470.
78. Rudzinska MA,Trager W, Bray RS. Pinocytotic uptake and the digestion of hemoglobin in malaria parasites.J Protozool 1991; 12: 563-576.
79. Jacobs GH, Oduola AMJ, Kyle DE, Milhous WK, Martin SK,Aikawa M. Ultrastructural study of the effects of chloroquine and verapamil on plasmodium falciparum.Am J Trop Med Hyg 1988; 39: 15-20.
80. YAyon A,TimbeRg R, Friedman S, Ginsburg H. Effects of chloroquine on the feeding mechanism of the intraerythrocytic human malarial parasite plasmodium falciparum.J Protozool. 1984; 31: 367-372.
81. + antiport of plasmodium falciparum membrane.J Cell Physiol 1993; 154:527-534.
82. Francis SE, Gluzman IY, OksmAn A et al. Molecular characterization and inhibition of a plasmodium falciparum aspartic hemoglobinase. EMBO J 1994; 13: 306-317.
83. Karcz SR, Herrmann VR, Cowman AR Cloning and characterization of a vacuolar atpase-a subunit homologue from plasmodium falciparum. Mol Biochem Parasitol 1993; 58: 333-344.
84. Karcz SR, Herrmann VR,Trottein F, Cowman AF. Cloning and characterization of the vacuolar atpase B subunit from plasmodium faldparum. Mol Biochem Parasitol 1994; 65: 123-133.