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.