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

被引：1

作者：

Tat'yanenko, L. V. ^{[1
]}

Khakina, E. A. ^{[1
]}

Zhilenkov, A. V. ^{[1
]}

Troshin, P. A. ^{[1
]}

Dobrokhotova, O. V. ^{[1
]}

Pikhteleva, I. Yu. ^{[1
]}

Kotel'nikov, A. I. ^{[1
]}

机构：

[1] Russian Acad Sci, Inst Problems Chem Phys, Chernogolovka, Moscow Region, Russia

来源：

BULLETIN OF EXPERIMENTAL BIOLOGY AND MEDICINE | 2017年 / 163卷 / 03期

关键词：

Ca2+-Mg2+-ATPase of the sarcoplasmic reticulum; cGMP phosphodiesterase; inhibition; fullerene derivatives; CHLOROFULLERENE C60CL6; COMPLEXES;

D O I：

10.1007/s10517-017-3794-y

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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 5x10(-5) M completely inhibited hydrolytic and transport functions of Ca2+-ATPase. These compounds in a concentration of 5x10(-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=2.3x10(-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=7x10(-6) M). These results allow us to expect antimetastatic, antiaggregatory, antihypertensive and vasodilative activity of the studied compounds.

引用

页码：321 / 325

页数：5

共 15 条

[1]

BEREZIN IV, 1973, PRACTICAL COURSE CHE, P77

[2] Cyclic GMP phosphodiesterase-5: Target of sildenafil [J].

Corbin, JD ;

Francis, SH .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (20) :13729-13732

[3]

FIDLER IJ, 1990, CANCER RES, V50, P6130

[4]

Granik VG, 2004, NEW WAY DRUG DEV

[5]

HONN KV, 1983, P SOC EXP BIOL MED, V174, P16

[6] Phosphodiesterase: overview of protein structures, potential therapeutic applications and recent progress in drug development [J].

Jeon, YH ;

Heo, YS ;

Kim, CM ;

Hyun, YL ;

Lee, TG ;

Ro, S ;

Cho, JM .

CELLULAR AND MOLECULAR LIFE SCIENCES, 2005, 62 (11) :1198-1220

[7] Highly selective reactions of C60Cl6 with thiols for the synthesis of functionalized [60]fullerene derivatives [J].

Khakina, Ekaterina A. ;

Yurkova, Anastasiya A. ;

Peregudov, Alexander S. ;

Troyanov, Sergey I. ;

Trush, Vyacheslav V. ;

Vovk, Andrey I. ;

Mumyatov, Alexander V. ;

Martynenko, Vyacheslav M. ;

Balzarini, Jan ;

Troshin, Pavel A. .

CHEMICAL COMMUNICATIONS, 2012, 48 (57) :7158-7160

[8] Facile preparation of amine and amino acid adducts of [60]fullerene using chlorofullerene C60Cl6 as a precursor [J].

Kornev, Alexey B. ;

Khakina, Ekaterina A. ;

Troyanov, Sergey I. ;

Kushch, Alla A. ;

Peregudov, Alexander ;

Vasilchenko, Alexey ;

Deryabin, Dmitry G. ;

Martynenko, Vyacheslav M. ;

Troshin, Pavel A. .

CHEMICAL COMMUNICATIONS, 2012, 48 (44) :5461-5463

[9]

RITOV VB, 1977, DOKL AKAD NAUK SSSR+, V233, P730

[10] The plasma membrane Ca2+-ATPase in spontaneously hypertensive rats [J].

Roufogalis, BD ;

Chen, S ;

Kable, EPW ;

Kuo, TH ;

Monteith, GR .

NA/K-ATPASE AND RELATED TRANSPORT ATPASES: STRUCTURE, MECHANISM, AND REGULATION, 1997, 834 :673-675

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