Conference publications


XXIV conference

The development of a new transport systems based on positively charged trans-membrane channels

Kasumov Kh.M.

Baku, F. Khoysky St., 98, Azerbaijan

2 pp. (accepted)

The development of new efficient systems in selective transport of ions and organic substances into living cells is one of most important problem of the clinical medicine. Pathological processes at the human organism at first take defections of ionic channels functioning in cell membranes [1, 6, 11]. It's known, that channels functioning at muscle cell's membranes capable transfer ions of Na+, K+, Ca ++ and monocarbohydrates with definite selectivity for providing the processes of glycolysis and oxidizing phosphorilation for the synthesis of macroergic substances with high chemical energy as ATP, creatin-phosphat etc. [2, 5, 10]. It's well known, that at the pathological processes (ishemia, stenocardia, dropped heart beats, miocardian infarction) the heart muscle sharply inhibits potassium and calcium conductivity and membrane conductivity for carbohydrates [12]. Due to this case at the pathology skeletal muscles inhibit process of absorption of carbohydrates and rising activity of membrane-linked enzymes. Also organism needs ions, carbohydrates and organic substances, so channels of muscle cells begin to work more intensive [3]. Anyway specific activity of native channels work is limited, thus they do not have capability in time-unit to bring essential quality of organic substances to muscle cells. So it is necessary to activate the work of native cell channels by exogenic substances that are capable to form additional cation-selective channels in muscle cells membranes. As a result of it is necessary to create the new selective transfer system of ions and substances into cell by exogenic carriers. Considering this, it's necessary to solve this problem by search of substances with known molecular mechanism of action that have high affinity to membranes and form ionic channels in cell membranes. Among these substances there are membrane-active channel-forming polyene antibiotics (PA) [4]. The main attention at this paper is the search of new transfer system, where membrane-active channel-forming positive charged PA-molecules are used. PA are the single group of substances in the nature that create molecular-size structural channels in cell membranes. We schedule to research by way of aromatic heptaene PA- levorin. This antibiotic subsists the few positive charged groups in its structure. In spite of presence of two positive charges in the chemical structure of levorin molecule there is selective conductance for cations in the membranes. Using a channel-forming levorin’s molecule may induce formation additional conductive channels in the muscle cell membranes. By involving levorin and its derivatives into membranes is capable to give effect of transmembrane transport of ions and carbohydrates that are so necessary in heart pathology. The synthesis of levorin's derivatives is necessary at first for solving question: "How does structural modification of levorin effect on physico-chemical properties of this molecule in the membranes?" and by the second side for creation transport system with the aim of transfer energy-dependent substratums (potassium, calcium ions and monocarbohydrates) into cells. The research of physico-chemical membrane's characteristics at the presence of levorin and its derivatives may create new pharmacological preparates that are effecient in the therapy of heart diseases like ishemia, stenocardia, dropped heart beats, miocardian infarction. Our preliminary researches show that stability, biological activity and efficiency of antibiotic’s work in water solution depends not only from antibiotic’s chemical structure, but from solvent’s type in which original antibiotic is dissolved. So, the maximal efficiency of antibiotics is observed at the dimethylsulfoxide (DMSO) solution [7, 8]. We suggest that molecule of levorine may be efficient in complex with DMSO at this pathology, because among of PA levorin is one of the most efficient compounds. It’s capable to change membrane’s conductivity at very small concentration 10-9–10-8 M. The number of conducting channels in the membrane depends on antibiotic concentration. The receiving of PA-derivatives by chemical modification of different parts in lacton ring molecule and research of physico-chemical properties on bilayer lipid membranes gives the unique possibility for theoretical basis of new antibiotic’s synthesis with known therapeutic properties.


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