O. V. Maliuk¹*, T. O. Veklich¹, O. V. Tsymbalyuk², O. V. Bevza¹,
S. O. Cherenok³, A. I. Selikhova³, V. I. Kalchenko³, S. O. Kosterin¹

¹Palladin Institute of Biochemistry, National Academy of Sciences
of Ukraine, Kyiv, Ukraine;
*e-mail: sanya2000ua@gmail.com;
²Educational and Scientific Institute of High Technologies,
Taras Shevchenko National University of Kyiv, Kyiv, Ukraine;
³Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine

Received: 29 May 2025; Revised: 18 July 2025;
Accepted: 12 September 2025; Available on-line: 17 September2025

Thiacalix[4]arene C-1193 (25,27-dibutoxythiacalix[4]arene-bis-hydroxymethylphosphonic acid) was shown to inhibit the activity of Na⁺,K⁺-ATPase with a high efficiency (І_0.5 = 42.1 ± 0.6 nM) with no effect on the activity of Mg²⁺-ATPase, Са²⁺-ATPase and Са²⁺,Mg²⁺-ATPase in the plasma membrane fraction of rat uterine smooth muscle cells. The kinetic regularities of the C-1193 inhibitory effect on Na⁺,K⁺-ATPase activity were investigated. It was demonstrated that C-1193 increased the enzyme activation constant by Na⁺ but not by K⁺ ions. The contractile activity of the rat uterine horns was investigated by tenzometric methods with the use of longitudinal uterine smooth muscle strips with intact endometrium. С-1193 induced a considerable increase in the amplitude of the acetylcholine-induced contractions as well as the maximal velocity of the contraction and relaxation phases. No effect of С-1193 on contractive activity induced by the selective agonist of М₃-cholinoreceptors cevimeline was observed. The results of computer simulation showed that С-1193inhibitory effect must be related to the cooperative action of methylene bisphosphonate fragments on the upper rim of the calixarene platform, and the linker sulfur atoms of calixarene “cup” on the Na⁺,K⁺-ATPase macrostructure.

Keywords: computer simulation, docking, K+-АТРase, myometrium, Na+, plasma membrane, smooth muscle cell, thiacalix[4]arenes