Effects of Covalent Conjugates of Fullerene Derivatives with Xanthene Dyes on Activity of Ca-ATPase of the Sarcoplasmic Reticulum.

The effects of the newly synthesized covalent conjugates of water-soluble fullerene derivatives (WSFD) with xanthene dyes: polyanionic WSFD-fluorescein (1), polycationic WSFD-fluorescein (2), polyanionic WSFD-eosin (3), and polyanionic WSFD (4), polycationic WSFD (5), fluorescein (6) and eosin (7), on activity of the membrane-bound Ca-ATPase of the sarcoplasmic reticulum (SR Ca-ATPase) were studied. Compounds 1, 3, 4, 6, and 7 inhibit the hydrolytic function of the enzyme, the inhibition constants for these compounds are Ki=1.3×10 M (1), Ki=4.7×10 M (3), Ki=2.5×10 M (4), Ki=6.1×10 M (6), and Ki=5.8×10 M (7). The effects of compounds 3, 6, and 7 on the hydrolytic function of the enzyme is competitive; compounds 1 and 4 are noncompetitive. Polycationic WSFD fluorescein (2) and polycationic WSFD (5) do not affect ATP hydrolysis, but inhibit active Ca transport in a concentration of 0.01 mM by 100±10 and 40±4%, respectively. Conjugates 1 and 3 completely inhibit the hydrolytic and transport functions of the enzyme in a concentration of 0.01 mM, and in a concentration of 0.001 mM inhibit active Ca transport by 60±6 and 55±6% uncoupling the hydrolytic and transport functions of SR Ca-ATPases. The obtained results demonstrate a significant effect of the studied compounds on the active transmembrane transfer of Ca and make it possible to predict the presence of antimetastatic and antiaggregatory activities of the studied compounds.