This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hawley, S. R.
Right arrow Articles by Ward, S. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hawley, S. R.
Right arrow Articles by Ward, S. A.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, March 1998, p. 682-686, Vol. 42, No. 3
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Relationship between Antimalarial Drug Activity, Accumulation, and Inhibition of Heme Polymerization in Plasmodium falciparum In Vitro

Shaun R. Hawley,1 Patrick G. Bray,2 Mathirut Mungthin,2 Jill D. Atkinson,2 Paul M. O'Neill,2 and Stephen A. Ward2,*

Department of Pharmacology and Therapeutics2 and Department of Human Anatomy and Cell Biology,1 University of Liverpool, Liverpool L69 3BX, United Kingdom

Received 25 September 1997/Returned for modification 5 November 1997/Accepted 10 December 1997

We have investigated the contribution of drug accumulation and inhibition of heme polymerization to the in vitro activities of a series of antimalarial drugs. Only those compounds exhibiting structural relatedness to the quinolines inhibited heme polymerization. We could find no direct correlation between in vitro activity against chloroquine-susceptible or chloroquine-resistant isolates and either inhibition of heme polymerization or cellular drug accumulation for the drugs studied. However, in vitro activity against a chloroquine-susceptible isolate but not a chloroquine-resistant isolate showed a significant correlation with inhibition of heme polymerization when the activity was normalized for the extent of drug accumulation. The importance of these observations to the rational design of new quinoline-type drugs and the level of agreement of these conclusions with current views on quinoline drug action and resistance are discussed.

* Corresponding author. Mailing address: Department of Pharmacology and Therapeutics, University of Liverpool, P.O. Box 147, Liverpool L69 3BX, United Kingdom. Phone: 0151 794 8219. Fax: 0151 794 8217. E-mail: saward{at}liv.ac.uk.

Antimicrobial Agents and Chemotherapy, March 1998, p. 682-686, Vol. 42, No. 3
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Roberts, L., Egan, T. J., Joiner, K. A., Hoppe, H. C. (2008). Differential Effects of Quinoline Antimalarials on Endocytosis in Plasmodium falciparum. Antimicrob. Agents Chemother. 52: 1840-1842 [Abstract] [Full Text]  
  • Pradines, B., Tall, A., Ramiandrasoa, F., Spiegel, A., Sokhna, C., Fusai, T., Mosnier, J., Daries, W., Trape, J. F., Kunesch, G., Parzy, D., Rogier, C. (2006). In vitro activity of iron-binding compounds against Senegalese isolates of Plasmodium falciparum. J Antimicrob Chemother 57: 1093-1099 [Abstract] [Full Text]  
  • Hatabu, T., Takada, T., Taguchi, N., Suzuki, M., Sato, K., Kano, S. (2005). Potent Plasmodicidal Activity of a Heat-Induced Reformulation of Deoxycholate-Amphotericin B (Fungizone) against Plasmodium falciparum. Antimicrob. Agents Chemother. 49: 493-496 [Abstract] [Full Text]  
  • Vargas, R. C., Tenreiro, S., Teixeira, M. C., Fernandes, A. R., Sa-Correia, I. (2004). Saccharomyces cerevisiae Multidrug Transporter Qdr2p (Yil121wp): Localization and Function as a Quinidine Resistance Determinant. Antimicrob. Agents Chemother. 48: 2531-2537 [Abstract] [Full Text]  
  • Pradines, B., Rolain, J. M., Ramiandrasoa, F., Fusai, T., Mosnier, J., Rogier, C., Daries, W., Baret, E., Kunesch, G., Le Bras, J., Parzy, D. (2002). Iron chelators as antimalarial agents: in vitro activity of dicatecholate against Plasmodium falciparum. J Antimicrob Chemother 50: 177-187 [Abstract] [Full Text]  
  • Cooper, R. A., Ferdig, M. T., Su, X.-Z., Ursos, L. M. B., Mu, J., Nomura, T., Fujioka, H., Fidock, D. A., Roepe, P. D., Wellems, T. E. (2002). 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. 61: 35-42 [Abstract] [Full Text]  
  • Vennerstrom, J. L., Nuzum, E. O., Miller, R. E., Dorn, A., Gerena, L., Dande, P. A., Ellis, W. Y., Ridley, R. G., Milhous, W. K. (1999). 8-Aminoquinolines Active against Blood Stage Plasmodium falciparum In Vitro Inhibit Hematin Polymerization. Antimicrob. Agents Chemother. 43: 598-602 [Abstract] [Full Text]  
  • Sullivan Jr., D. J., Matile, H., Ridley, R. G., Goldberg, D. E. (1998). A Common Mechanism for Blockade of Heme Polymerization by Antimalarial Quinolines. J. Biol. Chem. 273: 31103-31107 [Abstract] [Full Text]  
  • Lopez-Ribot, J. L., McAtee, R. K., Lee, L. N., Kirkpatrick, W. R., White, T. C., Sanglard, D., Patterson, T. F. (1998). Distinct Patterns of Gene Expression Associated with Development of Fluconazole Resistance in Serial Candida albicans Isolates from Human Immunodeficiency Virus-Infected Patients with Oropharyngeal Candidiasis. Antimicrob. Agents Chemother. 42: 2932-2937 [Abstract] [Full Text]  
  • Mungthin, M., Bray, P. G., Ridley, R. G., Ward, S. A. (1998). Central Role of Hemoglobin Degradation in Mechanisms of Action of 4-Aminoquinolines, Quinoline Methanols, and Phenanthrene Methanols. Antimicrob. Agents Chemother. 42: 2973-2977 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»