Thiacalix[4]arenes Remove the Inhibitory Effects of Zn Cations on the Myosin ATPase Activity

Abstract

Numerous female reproductive abnormalities are caused by uterine smooth muscle (myometrium) disorders. Heavy metals have an adverse effect on the contractility of the uterine smooth muscle. Although zinc is an essential biogenic element for most of the organisms, high doses of this element are toxic. The study of 0.5−5 mM Zn2+ effect on myosin S1 ATPase activity from the uterus found that 5 mM Zn2+ cations have the most pronounced inhibitory effect. The calculation of the kinetic parameters (Km and Vmax, ATP) revealed that the apparent maximum velocity of the hydrolysis ATP catalyzed by myosin in the presence of 5 mM Zn2+ decreased by 1.6 times. The value of Кm for ATP hydrolysis by myosin S1 in the presence of Zn2+ does not change statistically, although it tends to decrease. It was determined that uterine myosin S1 ATPase activity does not depend on the concentration of Mg2+ in the presence of 5 mM Zn2+. Also, it was demonstrated that tetrahydroxythiacalix[4]arene-tetrasulfosphonate (C-798) and tetrahydroxythiacalix[4]arene-tetraphosphonate (C-800) restored myosin S1 ATPase activity to the control level in the presence of 5 mM Zn2+. One of the most probable mechanisms of restoring the action of these thiacalix[4]arenes protective effect is based on its ability to chelate heavy metal cations from the incubation medium. The molecular docking of C-798 and C-800 into the myosin S1 region showed that these thiacalix[4]arenes could interact with Zn cation bond by myosin amino acid residues near the ATPase active site. Therefore, thiacalix[4]arenes may weaken the interaction between this cation and myosin S1. It was speculated that the obtained results could be used for further research with the aim of using this thiacalix[4]arenes as pharmacological compounds in the case of poisoning with high concentrations of zinc.

Тhiacalix[4]arene phosphonate C-800 as a novel fluorescent probe for zinc in living cells

“…It is well known that the sulfur atoms together with oxygen atoms at the lower rim can form five-membered chelate type complexes with zinc and other transitional metals [19,20]. Our attention was drawn to the thiacalіx [4]arenе phosphonous acids, with which we have been working for many years and obtained interesting results on their ability to eliminate the inhibitory effect of heavy metals, including Zn 2+ on the activity of myometrial myosin ATPase [21].…”