123363-40-6Relevant academic research and scientific papers
Structure-activity relationships for the Ca2+-releasing activity of 6-hydroxy-β-carboline analogues in skeletal muscle sarcoplasmic reticulum - The effects of halogen substitution at C-5 and C-7
Seino-Umeda, Asami,Ishibashi, Masami,Kobayashi, Jun'ichi,Ohizumi, Yasushi
, p. 517 - 521 (2000)
This study of structure-activity relationships of 6-hydroxy-β-carboline analogues has been performed on the basis of quantitative measurement of Ca2+-releasing activity in the sarcoplasmic reticulum of skinned fibres of skeletal muscle. Substitution of halogens for hydrogens at the C-5 and C-7 positions and further introduction of a methyl group into the N-9 position of 6-hydroxy-β-carboline resulted in Ca2+-releasing activity. The 50% effective concentrations of 5,7-dibromoeudistomin D, 5,7-dichloroeudistomin D, 5,7-diiodoeudistomin D, 9-methyl-5,7-dibromoeudistomin D, 9-methyl-5,7-dichloroeudistomin D, 9-methyl-5,7-diiodoeudistomin D, and caffeine were 5.6 x 10-6, 6.3 x 10-6, 7.8 x 10-6, 2.1 x 10-6, 2.0 x 10-5, 3.7 x 10-5, and 4.7 x 10-4 M, respectively, indicating that these analogues are 10-200 times more potent than caffeine. Substitution of bromine by chlorine or iodine at the C-5 and C-7 positions markedly reduced the activity of the analogues with a methyl group at the N-9 position. These results suggest that halogens at the C-5 and C-7 positions in the β-carboline skeleton are essential for Ca2+-releasing activity and that an N-9 methyl group also affects the activity of these analogues. Thus, these 6-hydroxy-β-carboline analogues might become powerful tools for studying the molecular mechanism of Ca2+ release in the sarcoplasmic reticulum.
