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Review

Quinoline antimalarials

Pages 185-209 | Published online: 25 Feb 2005

Bibliography

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  • ••This paper reports on novel 8-aminoquinolines withrelatively strong blood-stage activity and with evidence suggesting a possibly similar mechanism of action to chloroquine.
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  • ••A study of the effect of chloroquine and verapamil onvacuolar pH in live single parasites.
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  • ••A study that provides definitive evidence that the activity ofchloroquine is dependent on haemoglobin degradation in the parasite.
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  • ••This paper provides a detailed analysis of drug accumula-tion in chloroquine sensitive and resistant parasites and shows that specific, saturable chloroquine binding occurs, which is dependent on haemoglobin degradation in the parasite. Reduced binding occurs in resistant parasites.
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  • •A detailed investigation of chloroquine resistance, indicating that resistance results from decreased binding of drug to haematin and not due to decreased activity of a putative chloroquine importer.
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  • •A paper indicating a relationship between strength of haematin-drug binding, I3-haematin inhibitory potency and antiplasmodial activity of a series of quinoline drugs.
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  • ••This paper presents an alternative hypothesis for the modeof action of quinoline antimalarials, suggesting that binding of drugs to haematin inhibits its detoxification by glutathione-dependent degradation in the cytosol.
  • LORIA P, MILLERS, FOLEY M, TILLEY L: Inhibition of the peroxidative degradation of haem as the basis of action of chloroquine and other quinoline antimalari-als. Biochem. J. (1999) 339:363–370.
  • ••This paper presents another alternative hypothesis for themode of action of quinoline antimalarials, suggesting that binding of drugs to haematin inhibits its detoxification by peroxide-dependent degradation in the food vacuole.
  • EGAN TJ, ROSS DC, ADAMS PA: Quinoline anti-malarial drugs inhibit spontaneous formation of 13-haematin (malaria pigment). FEBS Lett. (1994) 352:54–57.
  • •The original paper showing that chloroquine inhibits I3-haematin formation by direct interaction with haematin under synthetic, protein-free conditions.
  • SULLIVAN DJ, GLUZMAN IY, RUSSELL DG, GOLDBERG DE: On the molecular mechanism of chloroquine's antimalarial action. Proc. Natl. Acad. Sci. USA (1996) 93 :11865–11870.
  • •A paper indicating that I3-haematin formation is inhibited by interaction of haematin-chloroquine complex with the growing pigment crystal (assumed to be a polymer at the time) and showing that this occurs even when initiated with histidine rich protein.
  • SULLIVAN DJ, MATILE H, RIDLEY RG, GOLDBERG DE: A common mechanism for blockade of haem polymeri-sation by antimalarial quinolines. J. Biol. Chem. (1998) 273:31103–31107.
  • BASILICO N, PAGANI E, MONTI D, OLLIARO P, TARAMELLI D: A microtitre-based method for measuring the haem polymerisation inhibitory activity (HPIA) of antimalarial drugs. J Antimicr. Chemother. (1998) 42:55–60.
  • EGAN TJ, HUNTER R, KASCHULA CH, MARQUES HM, MISPLON A, WALDEN J: Structure-function relation-ships in aminoquinolines: effect of amino and chloro groups on quinoline-haematin complex formation, inhibition of 13-haematin formation and antiplasmo-dial activity. J Med. Chem (2000) 43:283–291.
  • ••A detailed investigation of structure-function relationshipsin chloroquine and establishing minimal structural require-ments for association with haematin, inhibition of I3-haematin formation and antiplasmodial activity.
  • VIPPAGUNTA SR, DORN A, MATILE H et al.: Structural specificity of chloroquine-haematin binding related to inhibition of haematin polymerisation and parasite growth. J. Med. Chem. (1999) 42:4630–4639.
  • ••A detailed investigation of the effect of quinoline ringsubstituents on the association of quinolines with haematin, their I3-haematin inhibitory potency and antiplasmodial activity. It includes some molecular modeling.
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  • ••A paper showing that chloroquine analogues with shorter orlonger aminoalkyl side chains are fully active against chloro-quine resistant parasites.
  • DE D, KROGSTAD FM, BYERS LD, KROGSTAD DJ: Structure-activity relationships for an tiplasmo dial activity among 7-substituted 4-aminoquinolines. Med. Chem. (1998) 41 :4918–4926.
  • •A paper showing the effect of replacing the 7-chloro group on chloroquine and chloroquine analogues with other halogens.
  • O'NEILL PM, WILLOCK DJ, HAWLEY SR, BRAY PG, STORR RC, WARD SA, PARK BK: Synthesis, antimalarial activity and molecular modelling of tebuquine analogues. J Med. Chem (1997) 40:437–448.
  • •A paper establishing the relationship between quinoline accumulation in parasitised red blood cells and antiplasmo-dial activity.
  • RAYNES KJ, STOCKS PA, O'NEILL PM, PARK BK, WARD SA: New 4-aminoquinoline Mannich base antimalarials. 1. Effect of an alkyl substituent in the 5'-position of the 4t-hydroxyanilino side chain. J Med. Chem. (1999) 42:2747–2751.
  • ••Novel Mannich base compounds that show activity againstchloroquine resistant parasites and circumvent the toxicity problems of amodiaquine.
  • KOTECKA BM, BARLIN GB, EDSTEIN MD, RIECKMANN KH: New quinoline di-Mannich base compounds with greater antimalarial activity than chloroquine, amodiaquine or pyronaridine. Antimicr. Agents Chemother. (1997) 41:1369–1374.
  • ••Novel Mannich base compounds related to both amodia-quine and pyronaridine in structure and which circumvent chloroquine resistance and amodiaquine-like toxicity.
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