STRUCTURE-ACTIVITY RELATIONSHIP FOR THE INHIBITION OF CARDIAC SARCOPLASMIC-RETICULUM CA(2+)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) an d 2,3-(OCH3)(2)-1.4-naphthoquinone (2,3diOmeNQ)), differing for the pr esence of electrophilic groups in orto position in respect of quinone mojety and for hydroxylation in C5, were tested on Ca(2+)ATPase activi ty of cardiac sarcoplasmic reticulum membrane vesicles. The 2-unsubsti tuted quinone, juglone, was a potent inhibitor of Ca(2+)ATPase activit y, while the 2-methyl-substituted quinones, plumbagine and menadione, inhibited the enzyme activity only after a sufficiently long preincuba tion time 2,3DiOMeNQ did not affect Ca2+ ATPase activity at all. Hydro xylation in C5 was responsible for the type of inhibition, making it i rreversible. A direct interaction cf the electrophilic naphthoquinones with -SH groups of the enzyme is suggested.