Effects of Covalent Conjugates of Fullerene Derivatives with Xanthene Dyes on Activity of [Ca.sup.2+]-ATPase of the Sarcoplasmic Reticulum

• Published in: Bulletin of experimental biology and medicine 2020-05, Vol.169 (1), p.89
• Main Authors: Tatyanenko, L.V, Pokidova, O.V, Goryachev, N.S, Kraevaya, O.A, Khakina, E.A, Belik, A.Yu, Rybkin, A.Yu, Dobrokhotova, O.V, Pikhteleva, I.Yu, Troshin, P.A, Kotelnikov, A.I
• Format: Article
• Language: English
• Subjects: Adenosine triphosphatase; Analysis; Ethylenediaminetetraacetic acid; Fluorescein; Hydrolysis
• ISSN: 0007-4888
• DOI: 10.1007/s10517-020-04831-8

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.sup.2+]-ATPase of the sarcoplasmic reticulum (SR [Ca.sup.2+]-ATPase) were studied. Compounds 1, 3, 4, 6, and 7 inhibit the hydrolytic function of the enzyme, the inhibition constants for these compounds are [K.sub.i] = 1.3 * [10.sup.-5] M (1), [K.sub.i] = 4.7 * [10.sup.-6] M (3), [K.sub.i] = 2.5 * [10.sup.-6] M (4), [K.sub.i] = 6.1 * [10.sup.-5] M (6), and [K.sub.i] = 5.8 * [10.sup.-6] 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.sup.2+] transport in a concentration of 0.01 mM by 100 [+ or -] 10 and 40 [+ or -] 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.sup.2+] transport by 60 [+ or -] 6 and 55 [+ or -] 6% uncoupling the hydrolytic and transport functions of SR [Ca.sup.2+]-ATPases. The obtained results demonstrate a significant effect of the studied compounds on the active transmembrane transfer of [Ca.sup.2+] and make it possible to predict the presence of antimetastatic and antiaggregatory activities of the studied compounds. Key Words: [Ca.sup.2+]-ATPase of the sarcoplasmic reticulum; xanthene dyes; fullerene derivatives; inhibition