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Biochem Pharmacol. 1992 Apr 1;43(7):1545-53.

Site of action of the antimalarial hydroxynaphthoquinone, 2-[trans-4-(4'-chlorophenyl) cyclohexyl]-3-hydroxy-1,4-naphthoquinone (566C80).

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Biochemical Sciences, Wellcome Research Laboratories, Beckenham, Kent, U.K.


The site of action of the antimalarial compound 2-[trans-4-(4'-chlorophenyl) cyclohexyl]-3-hydroxy-1,4-naphthoquinone (566C80), would appear to be the mitochondrial respiratory chain. Studies reported herein have demonstrated 566C80 to be a potent and selective mitochondrial inhibitor with mitochondria isolated from Plasmodium falciparum and P. yoelii. Selective assay of individual respiratory chain complexes has shown the primary site of action of 566C80 to be the cytochrome bc1 complex (Complex III): supportive evidence from difference spectroscopy indicates the site of inhibition to lie between cytochromes b and c1 of this complex. Using [14C]566C80, evidence is presented which suggests that 566C80 may become irreversibly bound to a polypeptide with an approximate molecular mass of 11,500 Da.

[Indexed for MEDLINE]

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