Structure-activity relationship for the inhibition of cardiac sarcoplasmic reticulum Ca2+ ATPase activity by naphthoquinones.
Four naphthoquinones (5-OH-1,4-naphthoquinone (juglone), 5-OH-2-CH3-1,4-naphthoquinone (plumbagine), 2-CH3-1,4-naphthoquinone (menadione) and 2,3-(OCH3)2-1,4-naphthoquinone (2,3diOmeNQ)), differing for the presence of electrophilic groups in orto position in respect of quinone mojety and for hydroxylation in C5, were tested on Ca2+ ATPase activity of cardiac sarcoplasmic reticulum membrane vesicles. The 2-unsubstituted quinone, juglone, was a potent inhibitor of Ca2+ ATPase activity, while the 2-methyl-substituted quinones, plumbagine and menadione, inhibited the enzyme activity only after a sufficiently long preincubation time 2,3DiOMeNQ did not affect Ca2+ ATPase activity at all. Hydroxylation in C5 was responsible for the type of inhibition, making it irreversible. A direct interaction of the electrophilic naphthoquinones with -SH groups of the enzyme is suggested.
Floreani
M
M
Department of Pharmacology, University of Padova, Italy.
Forlin
A
A
Bellin
S
S
Carpenedo
F
F
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D002417:Cattle; D009206:Myocardium / Q000201:enzymology* / Q000648:ultrastructure; D009285:Naphthoquinones / Q000737:chemistry / Q000494:pharmacology*; D012519:Sarcoplasmic Reticulum / Q000201:enzymology*; D013329:Structure-Activity Relationship
D009285:Naphthoquinones; D000252:Calcium-Transporting ATPases