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. 1988 Jun;32(6):793–798. doi: 10.1128/aac.32.6.793

Antimalarial agents: mechanisms of action.

P H Schlesinger 1, D J Krogstad 1, B L Herwaldt 1
PMCID: PMC172284  PMID: 3046479

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allison J. L., O'Brien R. L., Hahn F. E. DNA: reaction with chloroquine. Science. 1965 Sep 3;149(3688):1111–1113. doi: 10.1126/science.149.3688.1111. [DOI] [PubMed] [Google Scholar]
  2. Bzik D. J., Li W. B., Horii T., Inselburg J. Molecular cloning and sequence analysis of the Plasmodium falciparum dihydrofolate reductase-thymidylate synthase gene. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8360–8364. doi: 10.1073/pnas.84.23.8360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chou A. C., Chevli R., Fitch C. D. Ferriprotoporphyrin IX fulfills the criteria for identification as the chloroquine receptor of malaria parasites. Biochemistry. 1980 Apr 15;19(8):1543–1549. doi: 10.1021/bi00549a600. [DOI] [PubMed] [Google Scholar]
  4. Ciak J., Hahn F. E. Chloroquine: mode of action. Science. 1966 Jan 21;151(3708):347–349. doi: 10.1126/science.151.3708.347. [DOI] [PubMed] [Google Scholar]
  5. Cohen S. N., Yielding K. L. Inhibition of DNA and RNA polymerase reactions by chloroquine. Proc Natl Acad Sci U S A. 1965 Aug;54(2):521–527. doi: 10.1073/pnas.54.2.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. De Duve C., Wattiaux R. Functions of lysosomes. Annu Rev Physiol. 1966;28:435–492. doi: 10.1146/annurev.ph.28.030166.002251. [DOI] [PubMed] [Google Scholar]
  7. Divo A. A., Geary T. G., Jensen J. B. Oxygen- and time-dependent effects of antibiotics and selected mitochondrial inhibitors on Plasmodium falciparum in culture. Antimicrob Agents Chemother. 1985 Jan;27(1):21–27. doi: 10.1128/aac.27.1.21. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Farquhar M. G., Palade G. E. The Golgi apparatus (complex)-(1954-1981)-from artifact to center stage. J Cell Biol. 1981 Dec;91(3 Pt 2):77s–103s. doi: 10.1083/jcb.91.3.77s. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fitch C. D., Chevli R., Banyal H. S., Phillips G., Pfaller M. A., Krogstad D. J. Lysis of Plasmodium falciparum by ferriprotoporphyrin IX and a chloroquine-ferriprotoporphyrin IX complex. Antimicrob Agents Chemother. 1982 May;21(5):819–822. doi: 10.1128/aac.21.5.819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fitch C. D. Mode of action of antimalarial drugs. Ciba Found Symp. 1983;94:222–232. [PubMed] [Google Scholar]
  11. Forgac M., Cantley L., Wiedenmann B., Altstiel L., Branton D. Clathrin-coated vesicles contain an ATP-dependent proton pump. Proc Natl Acad Sci U S A. 1983 Mar;80(5):1300–1303. doi: 10.1073/pnas.80.5.1300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Geary T. G., Divo A. A., Bonanni L. C., Jensen J. B. Nutritional requirements of Plasmodium falciparum in culture. III. Further observations on essential nutrients and antimetabolites. J Protozool. 1985 Nov;32(4):608–613. doi: 10.1111/j.1550-7408.1985.tb03087.x. [DOI] [PubMed] [Google Scholar]
  13. Geary T. G., Divo A. A., Jensen J. B. Effect of calmodulin inhibitors on viability and mitochondrial potential of Plasmodium falciparum in culture. Antimicrob Agents Chemother. 1986 Nov;30(5):785–788. doi: 10.1128/aac.30.5.785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Geary T. G., Divo A. A., Jensen J. B. Nutritional requirements of Plasmodium falciparum in culture. II. Effects of antimetabolites in a semi-defined medium. J Protozool. 1985 Feb;32(1):65–69. doi: 10.1111/j.1550-7408.1985.tb03014.x. [DOI] [PubMed] [Google Scholar]
  15. Geary T. G., Jensen J. B. Effects of antibiotics on Plasmodium falciparum in vitro. Am J Trop Med Hyg. 1983 Mar;32(2):221–225. doi: 10.4269/ajtmh.1983.32.221. [DOI] [PubMed] [Google Scholar]
  16. Geary T. G., Jensen J. B. Lack of cross-resistance to 4-aminoquinolines in chloroquine-resistant Plasmodium falciparum in vitro. J Parasitol. 1983 Feb;69(1):97–105. [PubMed] [Google Scholar]
  17. Ginsburg H., Divo A. A., Geary T. G., Boland M. T., Jensen J. B. Effects of mitochondrial inhibitors on intraerythrocytic Plasmodium falciparum in in vitro cultures. J Protozool. 1986 Feb;33(1):121–125. doi: 10.1111/j.1550-7408.1986.tb05570.x. [DOI] [PubMed] [Google Scholar]
  18. Ginsburg H., Geary T. G. Current concepts and new ideas on the mechanism of action of quinoline-containing antimalarials. Biochem Pharmacol. 1987 May 15;36(10):1567–1576. doi: 10.1016/0006-2952(87)90038-4. [DOI] [PubMed] [Google Scholar]
  19. Gluzman I. Y., Schlesinger P. H., Krogstad D. J. Inoculum effect with chloroquine and Plasmodium falciparum. Antimicrob Agents Chemother. 1987 Jan;31(1):32–36. doi: 10.1128/aac.31.1.32. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Griffiths G., Simons K. The trans Golgi network: sorting at the exit site of the Golgi complex. Science. 1986 Oct 24;234(4775):438–443. doi: 10.1126/science.2945253. [DOI] [PubMed] [Google Scholar]
  21. Gyang F. N., Poole B., Trager W. Peptidases from Plasmodium falciparum cultured in vitro. Mol Biochem Parasitol. 1982 Apr;5(4):263–273. doi: 10.1016/0166-6851(82)90034-2. [DOI] [PubMed] [Google Scholar]
  22. Homewood C. A., Warhurst D. C., Peters W., Baggaley V. C. Lysosomes, pH and the anti-malarial action of chloroquine. Nature. 1972 Jan 7;235(5332):50–52. doi: 10.1038/235050a0. [DOI] [PubMed] [Google Scholar]
  23. Jacobs G. H., Aikawa M., Milhous W. K., Rabbege J. R. An ultrastructural study of the effects of mefloquine on malaria parasites. Am J Trop Med Hyg. 1987 Jan;36(1):9–14. doi: 10.4269/ajtmh.1987.36.9. [DOI] [PubMed] [Google Scholar]
  24. Kent C. Inhibition of myoblast fusion by lysosomotropic amines. Dev Biol. 1982 Mar;90(1):91–98. doi: 10.1016/0012-1606(82)90214-7. [DOI] [PubMed] [Google Scholar]
  25. Krogstad D. J., Schlesinger P. H. A perspective on antimalarial action: effects of weak bases on Plasmodium falciparum. Biochem Pharmacol. 1986 Feb 15;35(4):547–552. doi: 10.1016/0006-2952(86)90345-x. [DOI] [PubMed] [Google Scholar]
  26. Krogstad D. J., Schlesinger P. H. Acid-vesicle function, intracellular pathogens, and the action of chloroquine against Plasmodium falciparum. N Engl J Med. 1987 Aug 27;317(9):542–549. doi: 10.1056/NEJM198708273170905. [DOI] [PubMed] [Google Scholar]
  27. Krogstad D. J., Schlesinger P. H., Gluzman I. Y. Antimalarials increase vesicle pH in Plasmodium falciparum. J Cell Biol. 1985 Dec;101(6):2302–2309. doi: 10.1083/jcb.101.6.2302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Krogstad D. J., Schlesinger P. H., Herwaldt B. L. Antimalarial agents: mechanism of chloroquine resistance. Antimicrob Agents Chemother. 1988 Jun;32(6):799–801. doi: 10.1128/aac.32.6.799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Krogstad D. J., Schlesinger P. H. The basis of antimalarial action: non-weak base effects of chloroquine on acid vesicle pH. Am J Trop Med Hyg. 1987 Mar;36(2):213–220. doi: 10.4269/ajtmh.1987.36.213. [DOI] [PubMed] [Google Scholar]
  30. Krotoski W. A., Collins W. E., Bray R. S., Garnham P. C., Cogswell F. B., Gwadz R. W., Killick-Kendrick R., Wolf R., Sinden R., Koontz L. C. Demonstration of hypnozoites in sporozoite-transmitted Plasmodium vivax infection. Am J Trop Med Hyg. 1982 Nov;31(6):1291–1293. doi: 10.4269/ajtmh.1982.31.1291. [DOI] [PubMed] [Google Scholar]
  31. Krotoski W. A., Krotoski D. M., Garnham P. C., Bray R. S., Killick-Kendrick R., Draper C. C., Targett G. A., Guy M. W. Relapses in primate malaria: discovery of two populations of exoerythrocytic stages. Preliminary note. Br Med J. 1980 Jan 19;280(6208):153–154. doi: 10.1136/bmj.280.6208.153-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Krugliak M., Waldman Z., Ginsburg H. Gentamicin and amikacin repress the growth of Plasmodium falciparum in culture, probably by inhibiting a parasite acid phospholipase. Life Sci. 1987 Mar 30;40(13):1253–1257. doi: 10.1016/0024-3205(87)90581-9. [DOI] [PubMed] [Google Scholar]
  33. Lot T. Y., Bennett T. The effects of chronic chloroquine administration in growing chicks. Med Biol. 1982 Aug;60(4):210–216. [PubMed] [Google Scholar]
  34. Milhous W. K., Weatherly N. F., Bowdre J. H., Desjardins R. E. In vitro activities of and mechanisms of resistance to antifol antimalarial drugs. Antimicrob Agents Chemother. 1985 Apr;27(4):525–530. doi: 10.1128/aac.27.4.525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Neva F. A. Looking back for a view of the future: observations on immunity to induced malaria. Am J Trop Med Hyg. 1977 Nov;26(6 Pt 2):211–215. doi: 10.4269/ajtmh.1977.26.211. [DOI] [PubMed] [Google Scholar]
  36. Nickell S. P., Scheibel L. W., Cole G. A. Inhibition by cyclosporin A of rodent malaria in vivo and human malaria in vitro. Infect Immun. 1982 Sep;37(3):1093–1100. doi: 10.1128/iai.37.3.1093-1100.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. O'Brien R. L., Olenick J. G., Hahn F. E. Reactions of quinine, chloroquine, and quinacrine with DNA and their effects on the DNA and RNA polymerase reactions. Proc Natl Acad Sci U S A. 1966 Jun;55(6):1511–1517. doi: 10.1073/pnas.55.6.1511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Ohkuma S., Poole B. Fluorescence probe measurement of the intralysosomal pH in living cells and the perturbation of pH by various agents. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3327–3331. doi: 10.1073/pnas.75.7.3327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Pfaller M. A., Krogstad D. J. Imidazole and polyene activity against chloroquine-resistant Plasmodium falciparum. J Infect Dis. 1981 Oct;144(4):372–375. doi: 10.1093/infdis/144.4.372. [DOI] [PubMed] [Google Scholar]
  40. Phillips R. E., Warrell D. A., White N. J., Looareesuwan S., Karbwang J. Intravenous quinidine for the treatment of severe falciparum malaria. Clinical and pharmacokinetic studies. N Engl J Med. 1985 May 16;312(20):1273–1278. doi: 10.1056/NEJM198505163122001. [DOI] [PubMed] [Google Scholar]
  41. Poole B., Ohkuma S. Effect of weak bases on the intralysosomal pH in mouse peritoneal macrophages. J Cell Biol. 1981 Sep;90(3):665–669. doi: 10.1083/jcb.90.3.665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. ROTH T. F., PORTER K. R. YOLK PROTEIN UPTAKE IN THE OOCYTE OF THE MOSQUITO AEDES AEGYPTI. L. J Cell Biol. 1964 Feb;20:313–332. doi: 10.1083/jcb.20.2.313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Roos A., Boron W. F. Intracellular pH. Physiol Rev. 1981 Apr;61(2):296–434. doi: 10.1152/physrev.1981.61.2.296. [DOI] [PubMed] [Google Scholar]
  44. Rothman J. E., Fine R. E. Coated vesicles transport newly synthesized membrane glycoproteins from endoplasmic reticulum to plasma membrane in two successive stages. Proc Natl Acad Sci U S A. 1980 Feb;77(2):780–784. doi: 10.1073/pnas.77.2.780. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Rothman J. E. The golgi apparatus: two organelles in tandem. Science. 1981 Sep 11;213(4513):1212–1219. doi: 10.1126/science.7268428. [DOI] [PubMed] [Google Scholar]
  46. Schwartz A. L., Hollingdale M. R. Primaquine and lysosomotropic amines inhibit malaria sporozoite entry into human liver cells. Mol Biochem Parasitol. 1985 Mar;14(3):305–311. doi: 10.1016/0166-6851(85)90058-1. [DOI] [PubMed] [Google Scholar]
  47. Seaberg L. S., Parquette A. R., Gluzman I. Y., Phillips G. W., Jr, Brodasky T. F., Krogstad D. J. Clindamycin activity against chloroquine-resistant Plasmodium falciparum. J Infect Dis. 1984 Dec;150(6):904–911. doi: 10.1093/infdis/150.6.904. [DOI] [PubMed] [Google Scholar]
  48. Sly W. S., Fischer H. D. The phosphomannosyl recognition system for intracellular and intercellular transport of lysosomal enzymes. J Cell Biochem. 1982;18(1):67–85. doi: 10.1002/jcb.1982.240180107. [DOI] [PubMed] [Google Scholar]
  49. Smrkovski L. L., Buck R. L., Alcantara A. K., Rodriguez C. S., Uylangco C. V. Studies of resistance to chloroquine, quinine, amodiaquine and mefloquine among Philippine strains of Plasmodium falciparum. Trans R Soc Trop Med Hyg. 1985;79(1):37–41. doi: 10.1016/0035-9203(85)90228-7. [DOI] [PubMed] [Google Scholar]
  50. Stahl P., Schwartz A. L. Receptor-mediated endocytosis. J Clin Invest. 1986 Mar;77(3):657–662. doi: 10.1172/JCI112359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Stone D. K., Xie X. S., Racker E. An ATP-driven proton pump in clathrin-coated vesicles. J Biol Chem. 1983 Apr 10;258(7):4059–4062. [PubMed] [Google Scholar]
  52. Trager W., Tershakovec M., Chiang P. K., Cantoni G. L. Plasmodium falciparum: antimalarial activity in culture of sinefungin and other methylation inhibitors. Exp Parasitol. 1980 Aug;50(1):83–89. doi: 10.1016/0014-4894(80)90010-7. [DOI] [PubMed] [Google Scholar]
  53. Tycko B., Maxfield F. R. Rapid acidification of endocytic vesicles containing alpha 2-macroglobulin. Cell. 1982 Mar;28(3):643–651. doi: 10.1016/0092-8674(82)90219-7. [DOI] [PubMed] [Google Scholar]
  54. Vander Jagt D. L., Baack B. R., Hunsaker L. A. Purification and characterization of an aminopeptidase from Plasmodium falciparum. Mol Biochem Parasitol. 1984 Jan;10(1):45–54. doi: 10.1016/0166-6851(84)90017-3. [DOI] [PubMed] [Google Scholar]
  55. Vander Jagt D. L., Hunsaker L. A., Campos N. M. Characterization of a hemoglobin-degrading, low molecular weight protease from Plasmodium falciparum. Mol Biochem Parasitol. 1986 Mar;18(3):389–400. doi: 10.1016/0166-6851(86)90095-2. [DOI] [PubMed] [Google Scholar]
  56. Vander Jagt D. L., Hunsaker L. A., Campos N. M. Comparison of proteases from chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. Biochem Pharmacol. 1987 Oct 1;36(19):3285–3291. doi: 10.1016/0006-2952(87)90646-0. [DOI] [PubMed] [Google Scholar]
  57. Warhurst D. C. Antimalarial drugs: mode of action and resistance. J Antimicrob Chemother. 1986 Oct;18 (Suppl B):51–59. doi: 10.1093/jac/18.supplement_b.51. [DOI] [PubMed] [Google Scholar]
  58. Webster H. K., Whaun J. M. Antimalarial properties of bredinin. Prediction based on identification of differences in human host-parasite purine metabolism. J Clin Invest. 1982 Aug;70(2):461–469. doi: 10.1172/JCI110636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. White N. J., Looareesuwan S., Warrell D. A., Chongsuphajaisiddhi T., Bunnag D., Harinasuta T. Quinidine in falciparum malaria. Lancet. 1981 Nov 14;2(8255):1069–1071. doi: 10.1016/s0140-6736(81)91275-7. [DOI] [PubMed] [Google Scholar]
  60. Willingham M. C., Pastan I. The receptosome: an intermediate organelle of receptor mediated endocytosis in cultured fibroblasts. Cell. 1980 Aug;21(1):67–77. doi: 10.1016/0092-8674(80)90115-4. [DOI] [PubMed] [Google Scholar]
  61. Wyler D. J. Malaria--resurgence, resistance, and research (second of two parts). N Engl J Med. 1983 Apr 21;308(16):934–940. doi: 10.1056/NEJM198304213081605. [DOI] [PubMed] [Google Scholar]
  62. Yayon A., Cabantchik Z. I., Ginsburg H. Identification of the acidic compartment of Plasmodium falciparum-infected human erythrocytes as the target of the antimalarial drug chloroquine. EMBO J. 1984 Nov;3(11):2695–2700. doi: 10.1002/j.1460-2075.1984.tb02195.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Yayon A., Cabantchik Z. I., Ginsburg H. Susceptibility of human malaria parasites to chloroquine is pH dependent. Proc Natl Acad Sci U S A. 1985 May;82(9):2784–2788. doi: 10.1073/pnas.82.9.2784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. 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 Aug;31(3):367–372. doi: 10.1111/j.1550-7408.1984.tb02981.x. [DOI] [PubMed] [Google Scholar]
  65. Yayon A., Vande Waa J. A., Yayon M., Geary T. G., Jensen J. B. Stage-dependent effects of chloroquine on Plasmodium falciparum in vitro. J Protozool. 1983 Nov;30(4):642–647. doi: 10.1111/j.1550-7408.1983.tb05336.x. [DOI] [PubMed] [Google Scholar]
  66. Zarchin S., Krugliak M., Ginsburg H. Digestion of the host erythrocyte by malaria parasites is the primary target for quinoline-containing antimalarials. Biochem Pharmacol. 1986 Jul 15;35(14):2435–2442. doi: 10.1016/0006-2952(86)90473-9. [DOI] [PubMed] [Google Scholar]
  67. de Duve C., de Barsy T., Poole B., Trouet A., Tulkens P., Van Hoof F. Commentary. Lysosomotropic agents. Biochem Pharmacol. 1974 Sep 15;23(18):2495–2531. doi: 10.1016/0006-2952(74)90174-9. [DOI] [PubMed] [Google Scholar]

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