Effects of Fullerene Derivatives on Activity of Ca2+-ATPase of the Sarcoplasmic Reticulum and cGMP Phosphodiesterase

Abstract

We studied the effects of new water-soluble polysubstituted fullerene C60 (PFD) derivatives on activity of Ca²⁺-Mg²⁺ ATPase of the sarcoplasmic reticulum and cGMP phosphodiesterase. All examined fullerene derivatives inhibited activity of both enzymes. For instance, PFD-I, PFD-II, PFD-III, PFD-V, PFD-IX, PFD-X, and PFD-XI in a concentration of 5×10^—5 M completely inhibited hydrolytic and transport functions of Ca²⁺-ATPase. These compounds in a concentration of 5×10^—6 suppressed active transport of calcium ions by 51±5, 77±8, 52±5, 52±5, 100±10, 80±8, and 100±10%, respectively, and inhibited ATP hydrolysis by 31±3, 78±8, 18±2, 29±3, 78±8, 63±7, and 73±9%, respectively, uncoupling the hydrolytic and transport functions of the enzyme. PFD-I noncompetitive and reversibly reduced activity of Ca²⁺-ATPase (K_i=2.3×10^—6 M). All the studied fullerene derivatives (except for PFD-VII) inhibited cGMP phosphodiesterase by more than 80% in concentration of 10^—4 M and higher and by more than 50% in concentration of 10^—5 M. PFD-I is a non-competitive reversible inhibitor of cGMP phosphodiesterase (K_i=7×10^—6 M). These results allow us to expect antimetastatic, antiaggregatory, antihypertensive and vasodilative activity of the studied compounds.