Journal article
Selective Inhibitors of Human Lactate Dehydrogenases and Lactate Dehydrogenase from the Malarial Parasite Plasmodium falciparum
Journal of medicinal chemistry, Vol.41(20), pp.3879-3887
09/24/1998
DOI: 10.1021/jm980334n
PMID: 9748363
Abstract
Derivatives of the sesquiterpene 8-deoxyhemigossylic acid (2,3- dihydroxy-6-methyl-4-(1-methylethyl)-1-naphthoic acid) were synthesized that contained altered alkyl groups in the 4-position and contained alkyl or aralkyl groups in the 7-position. These substituted dihydroxynaphthoic acids are selective inhibitors of human lactate dehydrogenase-H (LDH-H) and LDH-M and of lactate dehydrogenase from the malarial parasite Plasmodium falciparum (pLDH). All inhibitors are competitive with the binding of NADH. Selectivity for LDH-H, LDH-M, or pLDH is strongly dependent upon the groups that are in the 4- and 7-positions of the dihydroxynaphthoic acid backbone. Dissociation constants as low as 50 nM were observed, with selectivity as high as 400- fold.
Details
- Title: Subtitle
- Selective Inhibitors of Human Lactate Dehydrogenases and Lactate Dehydrogenase from the Malarial Parasite Plasmodium falciparum
- Creators
- Lorraine M. Deck - University of New MexicoRobert E. Royer - University of New MexicoBrian B. Chamblee - University of New MexicoValerie M. Hernandez - University of New MexicoRichard R. Malone - University of New MexicoJose E. Torres - University of New MexicoLucy A. Hunsaker - University of New MexicoRobert C. Piper - University of New MexicoMichael T. Makler - University of New MexicoDavid L. VANDER JAGT - Departments of Chemistry and of Biochemistry and Molecular Biology, University of New Mexico School of Medicine,Albuquerque, New Mexico 87131, Institute of Molecular Biology, University of Oregon, Eugene, Oregon 97403, and Departmentof Pathology, Oregon Health Sciences University and Veterans Administration Medical Center, Portland, Oregon 97201
- Resource Type
- Journal article
- Publication Details
- Journal of medicinal chemistry, Vol.41(20), pp.3879-3887
- DOI
- 10.1021/jm980334n
- PMID
- 9748363
- NLM abbreviation
- J Med Chem
- ISSN
- 0022-2623
- eISSN
- 1520-4804
- Publisher
- American Chemical Society
- Language
- English
- Date published
- 09/24/1998
- Academic Unit
- Molecular Physiology and Biophysics; Medicine Administration; Internal Medicine
- Record Identifier
- 9984297601702771
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