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Relationship between Antimalarial Drug Activity, Accumulation, and Inhibition of Heme Polymerization in Plasmodium falciparum In Vitro
Open accessAbstract
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.
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Cited by
Egan, T. J., Hunter, R., Kaschula, C. H., Marques, H. M., Misplon, A., & Walden, J. (2000) · Journal of Medicinal Chemistry · doi:10.1021/jm990437l · Cited by 317
Kaschula, C. H., Egan, T. J., Hunter, R., Basilico, N., Parapini, S., Taramelli, D., Pasini, E., & Monti, D. (2002) · Journal of Medicinal Chemistry · doi:10.1021/jm020858u · Cited by 272
Lopez-Ribot, J. L., McAtee, R. K., Lee, L. N., Kirkpatrick, W. R., White, T. C., Sanglard, D., & Patterson, T. F. (1998) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.42.11.2932 · Cited by 210
Haemozoin: from melatonin pigment to drug target, diagnostic tool, and immune modulator
Hänscheid, T., Egan, T. J., & Grobusch, M. P. (2007) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(07)70238-4 · Cited by 128
Metadata
- Authors
- Hawley, S. R., Bray, P. G., Mungthin, M., Atkinson, J. D., O’Neill, P. M., & Ward, S. A.
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 1998-03
- Volume
- 42
- Issue
- 3
- Pages
- 682-686
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- OpenAlex
- W2157746760
- Cited by
- 213
- References
- 0
- FWCI
- 6.80
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: Relationship between Antimalarial Drug Activity, Accumulation, and Inhibition of Heme Polymerization in Plasmodium falciparum In Vitro. https://app.cochat.ai/papers/10.1128/aac.42.3.682
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- Hawley, S. R., Bray, P. G., Mungthin, M., Atkinson, J. D., O’Neill, P. M., & Ward, S. A. (1998). Relationship between Antimalarial Drug Activity, Accumulation, and Inhibition of Heme Polymerization in Plasmodium falciparum In Vitro. Antimicrobial Agents and Chemotherapy. https://doi.org/10.1128/aac.42.3.682
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
