ИСТИНА

In recent years, in many laboratories around the world, new compounds have been synthesized and studied in order to create therapeutic drugs with a mitochondrial focus. Mitochondria are key organelles that perform basic cellular functions and play a crucial role in signaling death and cell survival. Therefore, they represent an attractive target for targeted drug delivery for the treatment of metabolic, degenerative and other diseases. Due to the presence of a high negative potential on the inner membrane of mitochondria (120-180 mV), compounds based on penetrating cations, such as triphenylphosphonium, rhodamines and others, are synthesized to deliver biologically important compounds or drugs to the mitochondria. Previously, it was shown that such conjugates are capable of having the expected (antioxidant, pro-oxidant, photosensitizing, etc.) effect in various biological systems. At the same time, the number of scientific papers demonstrating the toxic effect of conjugates and lipophilic cations on cells and isolated mitochondria is growing. In this regard, it is very important to find out the mechanisms of action and the degree of influence of lipophilic cations on model and natural lipid membranes by the example of a number of triphenylphosphonium analogues. Similar studies with varying alkyl chain lengths have been carried out. It is known that an increase in the number of methylene groups in the alkyl leads to an increase in the hydrophobicity of the lipophilic cation and the manifestation of an uncoupling and antibacterial effect in lower concentrations. However, the introduction of various substituents into the phenyl rings of triphenylphosphonium may turn out to be a more promising way to modify the cation. Previously, we showed that the permeability through planar bilayer lipid membranes of butyl triphenylphosphonium analogues with halogen and methyl substituents varies by six orders of magnitude. Therefore, one can also expect significant differences in their uncoupling effect on biological and model membranes. The study of analogues with substitutions in phenyl rings and substitutions of phenyl rings with alkyls will help to identify cations that have minimal side effects in biological systems, but are effective vectors for the delivery of biologically important molecules to mitochondria.

Исследование аналогов с замещениями в фенильных кольцах и замещениями фенильных колец на алкилы поможет выявить катионы, оказывающие минимальные побочные действия в биологических системах, однако являющихся эффективными векторами для доставки биологически важных молекул в митохондрии.