Selected calix[4]arene as an effective modulator of mitochondrial function and smooth muscle contractility.

Macrocyclic nanocompounds, particularly calix[4]arenes, are attracting growing interest in biomedical and molecular biotechnology research. Calix[4]arene C-715, functionalized with trifluoroacetamide groups on the upper rim, does not affect Ca2+ transport systems of the plasma membrane or sarcoplasmic reticulum, nor the ATPase activity of the myosin head, suggesting a selective action on mitochondrial Ca2+ transport. This study investigated the effects of C-715 on electron transport chain activity, Ca2+ handling, and nitric oxide production in isolated mitochondria of uterine smooth muscle, alongside a mechanokinetic assessment of its influence on myometrial contractility. Colocalization of the calix[4]arene-FITC conjugate C-1308 with MitoTracker Orange CM-H2TMRos confirmed mitochondrial targeting in myocytes. Calix[4]arene C-715 (30 μM) suppressed NADH oxidation and, in a concentration-dependent manner (10-30 μM), reduced the efficiency of energy-dependent Ca2+ accumulation and reactive oxygen species generation in isolated mitochondria. At 30 μM, it also decreased NO production in both mitochondria and intact myocytes. At the same concentration, calix[4]arene C-715 increased the amplitude and frequency of spontaneous contractions in rat myometrial strips. Comprehensive mechanokinetic analysis demonstrated that the compound enhanced force, temporal, and impulse parameters of spontaneous contraction-relaxation cycles. Consistent with these effects, C-715 induced a reduction in the characteristic size of myocytes in suspension. These data indicate that calix[4]arene C-715, at micromolar concentrations, acts as an effective modulator of mitochondrial function and uterine smooth muscle contractility.