Deck L M, Royer R E, Chamblee B B, Hernandez V M, Malone R R, Torres J E, Hunsaker L A, Piper R C, Makler M T, Vander Jagt D L
Departments of Chemistry and of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131.
J Med Chem. 1998 Sep 24;41(20):3879-87. doi: 10.1021/jm980334n.
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.
合成了倍半萜8-脱氧半棉子酸（2,3-二羟基-6-甲基-4-(1-甲基乙基)-1-萘甲酸）的衍生物，这些衍生物在4-位含有改变的烷基，在7-位含有烷基或芳烷基。这些取代的二羟基萘甲酸是人乳酸脱氢酶-H（LDH-H）、LDH-M以及疟原虫恶性疟原虫乳酸脱氢酶（pLDH）的选择性抑制剂。所有抑制剂与NADH的结合具有竞争性。对LDH-H、LDH-M或pLDH的选择性强烈依赖于二羟基萘甲酸主链4-位和7-位的基团。观察到解离常数低至50 nM，选择性高达400倍。
