References

1. Gilles HM: Management of severe and complicated malaria, a practical handbook.

   World Health Organisation GENEVA 1991, 56.

2. Warhurst DC, Thomas SC: Pharmacology of the malaria parasite.

   Biochem Pharmacol 1975, 24:2047-56. PubMed Abstract | Publisher Full Text

3. Warhurst DC, Hockley DJ: The mode of action of chloroquine on Plasmodium berghei and P. cynomolgi.

   Nature 1967, 214:935-6. PubMed Abstract

4. Fitch CD: Plasmodium falciparum in owl monkeys: drug resistance and chloroquine binding capacity.

   Science 1970, 169:289-90. PubMed Abstract

5. Homewood CA, Warhurst DC, Peters W, Baggaley VC: Lysosomes, pH and the anti-malarial action of chloroquine.

   Nature 1972, 235:50-2. PubMed Abstract

6. Macomber PB, Sprinz H: Morphological effects of chloroquine on Plasmodium berghei in mice.

   Nature 1967, 214:937-9. PubMed Abstract

7. Chou AC, Chevli R, Fitch CD: Ferriprotoporphyrin IX fulfils the criteria for identification as the chloroquine receptor of malaria parasites.

   Biochemistry 1980, 19:1543-1549. PubMed Abstract

8. Pagola S, Stephens PW, Bohle DS, Kosar AD, Madsen SK: The structure of malaria pigment beta-haematin.

   Nature 2000, 404:307-10. PubMed Abstract | Publisher Full Text

9. Buttle GAH, Henry TA, Solomon W, Trevan JW, Gibbs EM: The action of the cinchona and certain other alkaloids in bird malaria.

   Biochemistry 1938, 32:47-58.

10. Taggart JV, Earle DP, Berliner RW, Zubrod CG, Welch WJ, Wise NB, Schroeder EF, London IM, Shannon JA: Studies on the chemotherapy of the human malarias. III. The physiological distribution and antimalarial activity of the cinchona alkaloids.

    J Clin Invest 1948, 27(Suppl):80-86.

11. Trager W, Jensen JB: Human malaria parasites in continuous culture.

    Science 1976, 193:673-5. PubMed Abstract

12. Warhurst DC: The quinine-haemin interaction and its relationship to antimalarial activity.

    Biochem Pharmacol 1981, 30:3323-3327. PubMed Abstract | Publisher Full Text

13. Wesche DL, Black J: A comparison of the antimalarial activity of the cinchona alkaloids against P. falciparum in vitro.

    J Trop Med Hyg 1990, 93:153-159. PubMed Abstract

14. Karle JM, Olmeda R, Gerena L, Milhous WK: Plasmodium falciparum: Role of absolute stereochemistry in the antimalarial activity of synthetic amino alcohol antimalarial agents.

    Exp Parasitol 1993, 76:345-351. PubMed Abstract | Publisher Full Text

15. Karle JM, Karle IL, Gerena L, Milhous WK: Stereochemical evaluation of the relative activities of the cinchona alkaloids against Plasmodium falciparum.

    Antimicrob Agents Chemother 1992, 36:1538-1544. PubMed Abstract

16. Oleksyn BJ, Suszko-Purzycka A, Dive G, Lamotte-Brasseur J: Molecular properties of Cinchona alkaloids: a theoretical approach.

    J Pharm Sci 1992, 81:122-127. PubMed Abstract

17. Karle JM, Karle IL: Crystal structure of (-)-mefloquine hydrochloride reveals consistency of configuration with biological activity.

    Antimicrob Agents Chemother 2002, 46:1529-1534. PubMed Abstract | Publisher Full Text | PubMed Central Full Text

18. Behere DV, Goff HM: High affinity binding of quinine to iron (III) porphyrin: novel formation of alkoxide complexes from alcohols and amines.

    J Am Chem Soc 1984, 106:4945-4950.

19. Egan TJ, Ross DC, Adams PA: Quinoline anti-malarial drugs inhibit spontaneous formation of beta-haematin (malaria pigment).

    FEBS Lett 1994, 352:54-57. PubMed Abstract | Publisher Full Text

20. Kubinyi H: Lipophilicity and drug activity.

    in Progress in Drug Research(Edited by: Jucker E). 1979, 23:97-198.

    Birkhauser (Basel)

21. Rekker RF: The hydrophobic fragmental constant. Its derivation and application.

    in The Hydrophobic Fragmental Constant(Edited by: Nauta WT, Rekker RF). 1977, 1:1-24.

    Elsevier, (Amsterdam)

22. Hansch C, Leo A: Exploring QSAR: Fundamentals and Applications in Chemistry and Biology".

    American Chemical Society, Washington, DC 1995, 1:120.

23. Scherrer RA, Howard SM: Use of distribution coefficients in quantitative structure-activity relationships.

    J Med Chem 1977, 20:53-58. PubMed Abstract

24. Brossi A, Uskokovic M, Gutzwiller J, Krettli AU, Brener Z: Antimalarial activity of natural, racemic and unnatural dihydroquinine, dihydroquinidine and their various racemic analogs in mice infected with Plasmodium berghei.

    Experientia 1971, 27:1100-1101. PubMed Abstract

25. Leo AJ, Hansch C: Role of hydrophobic effects in mechanistic QSAR.

    in Perspectives in Drug Discovery and Design(Edited by: Martin YC). 1999, 17:1-25. Publisher Full Text

26. Van der Waterbeemd H, Testa B: The parametrization of lipophilicity and other structural properties in drug design.

    Advances in Drug Research 1987, 16:85.

27. Yayon A, Cabantchik ZI, Ginsburg H: Identification of the acidic compartment of Plasmodium falciparum-infected human erythrocytes as the target of the antimalarial drug chloroquine.

    EMBO J 1984, 3:2695-700. PubMed Abstract

28. Krogstad DJ, Schlesinger PH: A perspective on antimalarial action: effects of weak bases on Plasmodium falciparum.

    Biochem Pharmacol 1986, 35:547-552. PubMed Abstract | Publisher Full Text

29. Hawley SR, Bray PG, Park BK, Ward SA: Amodiaquine accumulation in Plasmodium falciparum as a possible explanation for its superior antimalarial activity over chloroquine.

    Mol Biochem Parasitol 1996, 80:15-25. PubMed Abstract | Publisher Full Text

30. Avdeef A: pH-metric log P. 2: Refinement of partition coefficients and ionization constants of multiprotic substances.

    J Pharm Sci 1993, 82:183-190. PubMed Abstract

31. Chien YW, Lambert HJ, Karim A: Comparative binding of disopyramide phosphate and quinidine sulfate to human plasma proteins.

    J Pharm Sci 1974, 63:1877-1879. PubMed Abstract

32. Takacs-Novak K, Avdeef A: Interlaboratory study of log P determination by shake-flask and potentiometric methods.

    J Pharm Biomed Anal 1996, 14:1405-13. PubMed Abstract | Publisher Full Text

33. Parapini S, Basilico N, Pasini E, Egan TJ, Olliaro P, Taramelli D, Monti D: Standardization of the physicochemical parameters to assess in vitrothe beta-haematin inhibitory activity of antimalarial drugs.

    Exp Parasitol 2000, 96:249-56. PubMed Abstract | Publisher Full Text

34. Allinger NL: Conformational Analysis 130. MM2. A Hydrocarbon Force Field Utilizing V1 and V2 Torsional Terms.

    J Am Chem Soc 1977, 99:8127-8134.

    (MM+ is a HyperChem modification and extension of Norman Allinger's Molecular Mechanics program MM2)

35. Stewart JJP: Optimization of Parameters for Semi-empirical Methods. I. Method.

    J Comput Chem 1989, 10:209.

    PM3 is JJP Stewart's reparametrization of the AMI neglect of diatomic differential overlap (NDDO) approximation described in the above publication

36. Stewart JJP: Optimization of Parameters for Semi-empirical Methods. II. Applications.

    J Comput Chem 1989, 10:221.

37. Koenig DF: The structure of β-chlorohemin.

    Acta Crystallogr 1965, 18:663-673. PubMed Abstract | Publisher Full Text

38. Anderson WP, Edwards WD, Zerner MC: Calculated Spectra of Hydrated Ions of the First Transition Series.

    Inorg Chem 1986, 25:2728-2732.

    ZINDO/S is Michael Zerner's intermediate neglect of differential overlap (INDO) quantum mechanical method for electronic spectra of molecular systems containing transition metals, discussed in the above article.

39. Irwin JL, Irwin EM: Apparent dissociation exponents of quinine, pamaquine and a quinolylpiperidyl-carbinol; application of an extended pH scale.

    J Biol Chem 1948, 174:577-587.

40. Perrin DD: Dissociation constants of organic bases in aqueous solution.

    Butterworth's London 1965.

41. Prelog V, Hafliger O: Über China-Alkaloide 9. Über den einflussder Konfiguration auf die Basizitat und über die relative Konfiguration an den Kohlenstoffatomen 8 und 9.

    Helv Chim Acta 1950, 33:2021-2029.

42. Mannhold R, Dross KP, Rekker RF: Drug lipophilicity in QSAR practice: I. A comparison of experimental with calculative approaches.

    Quant Struct-Act Relat 1990, 9:21-28.

43. Lullmann H, Wehling M: The binding of drugs to different polar lipids in vitro.

    Biochem Pharmacol 1979, 28:3409-3415. PubMed Abstract | Publisher Full Text

44. Hansch C:

    in Comprehensive Medicinal Chemistry (Edited by: Hansch C). Pergamon press NY 1990, 2:159.

45. Hawley SR, Bray PG, O'Neill PM, Park BK, Ward SA: The role of drug accumulation in 4-aminoquinoline antimalarial potency. The influence of structural substitution and physicochemical properties.

    Biochem Pharmacol 1996, 52:723-733. PubMed Abstract | Publisher Full Text

46. Karle JM, Bhattacharjee AK: Stereoelectronic features of the cinchona alkaloids determine their differential antimalarial activity.

    Bioorg Med Chem 1999, 7:1769-1774. PubMed Abstract | Publisher Full Text

47. Egan TJ, Hunter R, Kaschula CH, Marques HM, Misplon A, Walden J: Structure-function relationships in aminoquinolines: effect of amino and chloro groups on quinoline-haematin complex formation, inhibition of beta-haematin formation, and antiplasmodial activity.

    J Med Chem 2000, 43:283-291. PubMed Abstract | Publisher Full Text

48. Moon RP, Bur D, Loetscher H, D'Arcy A, Tyas L, Oefner C, Grueninger-Leitch F, Mona D, Rupp K, Dorn A, Matile H, Certa U, Berry C, Kay J, Ridley RG: Studies on plasmepsins I and II from the malarial parasite Plasmodium falciparum and their exploitation as drug targets.

    Adv Exp Med Biol 1998, 436:397-406. PubMed Abstract

49. Bominaar EL, Ding XQ, Gismelseed A, Bill E, Winkler H, Trautwein AX, Nasri H, Fischer J, Weiss R: Structural, Mossbauer and EPR investigations on 2 oxidation states of a five-co-ordinate, high spin synthetic heme. Quantitative interpretation of zero-field parameters and large quadrupole splitting.

    Inorg Chem 1992, 31:1845-1854.

50. Egan TJ, Mavuso WW, Ross DC, Marques HM: Thermodynamic factors controlling the interaction of quinoline antimalarial drugs with ferriprotoporphyrin IX.

    J Inorg Biochem 1997, 68:137-145. PubMed Abstract | Publisher Full Text

51. Krogstad DJ, Gluzman IY, Kyle DE, Oduola AM, Martin SK, Milhous WK, Schlesinger PH: Efflux of chloroquine from Plasmodium falciparum: mechanism of chloroquine resistance.

    Science 1987, 238:1283-1285. PubMed Abstract

52. Oduola AM, Sowunmi A, Milhous W, Brewer TG, Kyle DE, Gerena L, Rossan RN, Salako LA, Schuster BG: In vitro and in vivo reversal of chloroquine-resistance in Plasmodium falciparum with promethazine.

    Am J Trop Med Hyg 1998, 58:625-629. PubMed Abstract | Publisher Full Text

53. Martiney JA, Cerami A, Slater AFG: Verapamil reversal of chloroquine-resistance in the malaria parasite Plasmodium falciparum is specific for resistant parasites and independent of the weak base effect.

    J Biol Chem 1995, 270:22393-22398. PubMed Abstract | Publisher Full Text

54. Bray PG, Hawley SR, Mungthin M, Ward SA: Physicochemical properties correlated with drug resistance and the reversal of drug resistance in Plasmodium falciparum.

    Mol Pharmacol 1996, 50:1559-1566. PubMed Abstract

55. Bhattacharjee AK, Kyle DE, Vennerstrom JL, Milhous WK: A 3D QSAR pharmacophore model and quantum chemical structure-activity analysis of chloroquine-resistance reversal.

    J Chem Inf Comput Sci 2002, 45:1212-20. Publisher Full Text

56. Fidock DA, Nomura T, Talley AK, Cooper RA, Dzekunov SM, Ferdig MT, Ursos LMB, Sidhu ABS, Naude B, Deitsch KW, Su XZ, Wooton JC, Roepe PD, Wellems TE: Mutations in the P. falciparum digestive vacuole transmembrane protein PFCRT and evidence for their role in chloroquine resistance.

    Molecular Cell 2000, 6:861-71. PubMed Abstract | Publisher Full Text

57. Djimde A, Doumbo OK, Cortese JF, Kayentao K, Doumbo S, Diourte Y, Dicko A, Su XZ, Nomura T, Fidock DA, Wellems TE, Plowe CV, Coulibaly D: A molecular marker for chloroquine-resistant falciparum malaria.

    N Engl J Med 2001, 344:257-63. PubMed Abstract | Publisher Full Text

58. Sidhu AB, Verdier-Pinard D, Fidock DA: Chloroquine resistance in Plasmodium falciparum malaria parasites conferred by pfcrt mutations.

    Science 2002, 298:210-3. PubMed Abstract | Publisher Full Text

59. Dutzler R, Campbell EB, Cadene M, Chait BT, MacKinnon R: X-ray structure of a ClC chloride channel at 3.0 Å reveals the molecular basis of anionselectivity.

    Nature 2002, 415:287-94. PubMed Abstract | Publisher Full Text

60. Zhang H, Howard EM, Roepe PD: Analysis of the antimalarial drug resistance protein Pfcrt in yeast.

    J Biol Chem 2002, 277:49767-75. PubMed Abstract | Publisher Full Text

61. Warhurst DC, Craig JC, Adagu IS: Lysosomes and drug resistance in malaria (Commentary).

    Lancet 2002, 360:1527-1529. PubMed Abstract | Publisher Full Text

62. National Cancer Institute Database [http://129.43.27.140/ncidb2/]
63. Moreau S, Perly B, Chachaty C, Deleuze C: A nuclear magnetic resonance study of the interactions of antimalarial drugs with porphyrins.

    Biochim Biophys Acta 1985, 840:107-16. PubMed Abstract | Publisher Full Text

64. Schulman SG, Threatte RM, Capomachia AC, Paul WL: Fluorescence of 6-methoxyquinoline, quinine and quinidine in aqueous media.

    J Pharm Sci 1974, 63:876-880. PubMed Abstract

65. Tsai RS, Carrupt PA, Testa B, El Tayar N, Gruenewaald G, Casey A: Influence of stereochemical factors on the partition coefficient of diastereomers.

    J Chem Research 1993, 1901-1920.

66. Allen RI, Box KJ, Comer JEA, Peake C, Tam KY: Multiwavelength spectrophotometric determination of acid dissociation constants of ionizable drugs.

    J Pharm Biomed Anal 1998, 17:699-712. PubMed Abstract | Publisher Full Text

67. Drzewiczak C, Suszko-Purzycka A, Skolik J: Correlation between structure and basicity of Cinchona alkaloids.

    Polish J Chem 1993, 67:45-52.

68. Drzewiczak C, Zalewski RI, Skolik J, Suszko-Purzycka A: Spectrophotometric determination of the second dissociation constant of Cinchona alkaloids.

    Polish J Chem 1993, 67:53-58.

69. Lepetit G: Die pH-abhängige Lipidlöslichkeit von Arzneistoffen.

    Pharmazie 1977, 32:289-291. PubMed Abstract

70. Hansch C, Anderson SM: The effect of intramolecular hydrophobic bonding on partition coefficients.

    J Org Chem 1967, 32:2583-2586.

71. Cassidy SL, Lympany PA, Henry JA: Lipid solubility of a series of drugs.

    J Pharm Pharmacol 1988, 40:130-132. PubMed Abstract

72. Unger SH, Chiang GH: Octanol-physiological buffer distribution coefficients of lipophilic amines and their correlation with biological activity.

    J Med Chem 1981, 24:262-270. PubMed Abstract

73. Warhurst DC, Steele JCP, Adagu IS, Craig JC, Cullander C: Hydroxychloroquine is much less active than chloroquine against chloroquine-resistant Plasmodium falciparum, in agreement with its physicochemical properties.

    J Antimicrob Chemother 2003, 52:188-93. PubMed Abstract | Publisher Full Text

74. Loyevsky M, John C, Zaloujnyi I, Gordeuk V: Aminothiol multidentate chelators as antimalarials.

    Biochem Pharmacol 1997, 54:451-8. PubMed Abstract | Publisher Full Text

75. Shanzer A, Libman J, Lytton SD, Glickstein H, Cabantchik ZI: Reversed siderophores act as antimalarial agents.

    Proc Natl Acad Sci U S A 1991, 88:6585-6589. PubMed Abstract | Publisher Full Text | PubMed Central Full Text

76. Kaschula CH, Egan TJ, Hunter R, Basilico N, Parapini S, Taramelli D, Pasini E, Monti D: Structure-activity relationships in 4-aminoquinoline antiplasmodials. The role of the group at the 7-position.

    J Med Chem 2002, 45:3531-3539. PubMed Abstract | Publisher Full Text

77. Warhurst DC: Antimalarial schizontocides: why a permease is necessary.

    Parasitol Today 1986, 2:331-334. Publisher Full Text

78. Warhurst DC: Mechanism of chloroquine-resistance in malaria.

    Parasitol Today 1988, 4:211-213. Publisher Full Text

79. Bray PG, Howells RE, Ritchie GY, Ward SA: Rapid chloroquine efflux phenotype in both chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum. A correlation of chloroquine sensitivity with energy-dependent drug accumulation.

    Biochem Pharmacol 1992, 44:1317-1324. PubMed Abstract | Publisher Full Text

80. 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, 113:1033-42. PubMed Abstract

81. Karcz S, Cowman AF: Similarities and differences between the multidrug resistance phenotype of mammalian tumor cells and chloroquine resistance in Plasmodium falciparum.

    Exp Parasitol 1991, 73:233-40. PubMed Abstract

82. Reed MB, Saliba KJ, Caruana SR, Kirk K, Cowman AF: Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparum.

    Nature 2000, 403:906-9. PubMed Abstract | Publisher Full Text

83. Duraisingh MT, Roper C, Walliker D, Warhurst DC: Increased sensitivity to the antimalarials mefloquine and artemisinin is conferred by mutations in the pfmdr1 gene of Plasmodium falciparum.

    Mol Microbiol 2000, 36:955-61. PubMed Abstract | Publisher Full Text

84. Price RN, Cassar C, Brockman A, Duraisingh M, van Vugt M, White NJ, Nosten F, Krishna S: The pfmdr1 gene is associated with a multidrug-resistant phenotype in Plasmodium falciparum from the western border of Thailand.

    Antimicrob Agents Chemother 1999, 43:2943-9. PubMed Abstract | Publisher Full Text | PubMed Central Full Text

85. Waller KA, Muhle RA, Ursos LM, Horrocks P, Verdier-Pinard D, Sidhu AB, Fujioka H, Roepe PD, Fidock DA: Chloroquine resistance modulated in vitro by expression levels of the Plasmodium falciparum chloroquine resistance transporter (PfCRT).

    J Biol Chem 2003.

    June 17, 2003. [Epub ahead of print]

86. Ursos LM, DuBay KF, Roepe PD: Antimalarial drugs influence the pH dependent solubility of heme via apparent nucleation phenomena.

    Mol Biochem Parasitol 2001, 12:11-17. Publisher Full Text

87. Ursos LM, Dzekunov SM, Roepe PD: The effects of chloroquine and verapamil on digestive vacuolar pH of P. falciparum either sensitive or resistant to chloroquine.

    Mol Biochem Parasitol 2000, 110:125-134. PubMed Abstract | Publisher Full Text

88. Dzekunov SM, Ursos LM, Roepe PD: Digestive vacuolar pH of intact intraerythrocytic P. falciparum either sensitive or resistant to chloroquine.

    Mol Biochem Parasitol 2000, 110:107-124. PubMed Abstract | Publisher Full Text

89. Bray PG, Saliba KJ, Davies JD, Spiller DG, White MR, Kirk K, Ward SA: Distribution of acridine orange fluorescence in Plasmodium falciparum-infected erythrocytes and its implications for the evaluation of digestive vacuole pH.

    Mol Biochem Parasitol 2002, 119:301-304. PubMed Abstract | Publisher Full Text

90. Cooper RA, Ferdig MT, Su XZ, Ursos LM, Mu J, Nomura T, Fujioka H, Fidock DA, Roepe PD, Wellems TE: 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 2002, 61:35-42. PubMed Abstract | Publisher Full Text