The effects of new fullerene derivatives on the functioning of the hydrolases sarcoplasmic reticulum (SR) Ca-ATPase and cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) were studied. Most of the fullerene derivatives studied were found to inhibit the activity of both enzymes. Thus, compounds PSF-1, PSF-II, and PSF-III completely inhibited Ca transport at a concentration of 0.009 mM but inhibited ATP hydrolysis by only 55 ± 6%, 42 ± 8%, and 60 ± 6% respectively, thus uncoupling the hydrolytic and transport functions of the enzyme. This induced changes in the extra- and intracellular Ca ion levels and affected adhesion of metastatic cells to the capillary endothelium. Compound PSF-III had noncompetitive, reversible effects on the hydrolytic function of SR Ca-ATPase with K = 1.6 × 10 M. All the fullerene derivatives studied inhibited cGMP PDE function and could induce an antiaggregation effect which resulted from accumulation of the cGMP PDE substrate, i.e., cGMP, which is a second messenger in living organisms. These results can be used to predict the potential therapeutic effects of the fullerene derivatives studied. [ABSTRACT FROM AUTHOR]