I. S. Forys¹, O. V. Tsymbalyuk², Yu. V. Danylovych¹, H. V. Danylovych¹*,
M. V. Rudnytska¹, R. V. Rodik³, S. O. Kosterin¹

¹Department of Muscle Biochemistry, Palladin Institute of Biochemistry,
National Academy of Sciences of Ukraine, Kyiv;
²Department of Molecular Biotechnology and Bioinformatics, Educational Scientific Institute
of High Technologies, Taras Shevchenko National University of Kyiv, Ukraine;
³Department of Chemistry of Macrocyclic Compounds, Institute of Organic Chemistry,
National Academy of Sciences of Ukraine, Kyiv;
*e-mail: danylovychanna@ukr.net

Received: 06 April 2026; Revised: 06 May 2026;
Accepted: 29 May 2026; Available on-line: 18 June 2026

Background. Identification of non-toxic exogenous compounds capable of selective influencing intracellular Ca²⁺-dependent processes and smooth muscle contractility remains an important task of molecular biotechnology. Calix[4]arenes are considered promising modulators of cellular functions, and calix[4]arene C-772 is suggested to selective effect mitochondrial Ca²⁺ handling. Objective. The aim of this study was to evaluate the effect of calix[4]arene C-772 on Ca²⁺ transport in mitochondria of uterine smooth muscle, nitric oxide production in myocytes, and the contractile activity of myometrial strips. Methods. Non-pregnant Wistar rats were used in experiments, confocal microscopy, spectrofluorimetry, flow cytometry, and mechanokinetic analysis were applied. Results. Mitochondrial localization of calix[4]arenes in myocytes was confirmed by colocalization of the сalix[4]arene–FITC conjugate C-1308 with Mitotracker Orange CM-H₂TMRos. Calix[4]arene C-772 (10 μM) interacted with cardiolipin in mitochondrial membranes, inhibited nitric oxide synthesis, reduced Ca²⁺ accumulation in isolated mitochondria and increased the amplitude of rat myometrial smooth muscle spontaneous contractions. Mechanokinetic analysis demonstrated increased force, velocity, and impulse parameters of contraction–relaxation cycles. Conclusions. These findings indicate that calix[4]arene C-772 at micromolar concentrations can serve as an effective modulator of mitochondrial functional activity and uterine smooth muscle contractility.

Keywords: calcium, calix[4]arene, cardiolipin, mitochondria, myometrium, nitric oxide, smooth muscle