Effects of Water-Soluble Polysubstituted Fullerene Derivatives on Sarcoplasmic Reticulum Ca2+-ATPase and Cyclic Guanosine Monophosphate Phosphodiesterase Activities

• Published in: Pharmaceutical chemistry journal 2013-11, Vol.47 (8), p.405-408
• Main Authors: Tat’yanenko, L. V., Kotel’nikova, R. A., Poletaeva, D. A., Dobrokhotova, O. V., Pikhteleva, I. Yu, Kornev, A. B., Khakina, E. A., Troshin, P. A., Kotel’nikov, A. I.
• Format: Article
• Language: English
• Subjects: Medicine; Organic Chemistry; Pharmacology/Toxicology; Pharmacy
• ISSN: 0091-150X; 1573-9031
• DOI: 10.1007/s11094-013-0969-3

The effects of new fullerene derivatives on the functioning of the hydrolases sarcoplasmic reticulum (SR) Ca 2+ -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 2+ 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 2+ 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 2+ -ATPase with K i  = 1.6 × 10 –6  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.