Thiacalix[4]arene chalcone amides effect on myometrium contraction

Abstract

Calixarenes are macrocyclic compounds, the biochemical effects of which are actively studied. In this study we synthesized thiacalix[4]arene chalcone amides С-1191 and С-1192, which have a sulfur atom in their structure and different spatial arrangement of chalcone amide groups, and studied their effect on myometrium functioning. Experiments were conducted with the use of rat uterine smooth muscles preparations, isolated myometrial mitochondria and permeabilized myometrial cells. The relative value of mitochondria membrane potential (Δψ) was assayed with a voltage-sensitive fluorescent probe TMRM. The spontaneous contractive activity was studied by tenzometric method followed by mechanokinetic analysis. It was shown that C-1191 and C-1192 induced mitochondria hyperpolarization and increased the basal tension of myometrium smooth muscle preparation. Thiacalix[4]arene С-1191 did not change the uterine cycle, but increased the force, velocity and impulse parameters of muscle contractive activity. On the contrary, С-1192 modified the uterine cycle considerably, increased the total efficiency of the myometrium spontaneous contractive activity and decreased the force, time and impulse parameters. It is concluded that changes in the mechanokinetic parameters of myometrial contractile activity induced by С-1191 and С-1192 are determined by the functional activity of mitochondria. Keywords: mechanokinetic analysis, mitochondria, mitochondria membrane potential, myometrial contractile activity, thiacalix[4]arene chalcone amides