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Abstract
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.