AT1-BLOCKING ACTIVITY IN THE VARIETY OF BIPHENYL-BEARING BENZIMIDAZOLE

Abstract

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It is known that angiotensin AT1-receptors play an important role in physiology and patophysiology of cardio-vascular system. This serves as evidence about the timeliness and reasonability of the directed search for new chemical compounds - blockers of AT1-receptors. With this objective, in accordance with evidential base in this field, the study for biphenyl-bearing derivatives of benzimidazoles is considered rather perspective. Purpose of the work was to investigate new biphenyl-bearing derivatives of benzimidazole for the presence of AT1-antagonistic activity using an experimental model of an isolated portal vein of a rat in vitro in modification. Materials and methods of the study: we have carried out the investigation using mature outbred rats of both genders weighed 200-250 g, in accordance with the principles of bioethics. We have studied the non-cumulative response of the drug on the agonist of angiotensin II AT receptors injection in concentration 0.01 µmol/l. Incubation of the compounds under study and the comparison drug, selective AT1-antagonist, valsartan in equimolar doses 10 µmol/l was carried out during 2 minutes, and then the response on angiotensin II was reevaluated. We judged the level of AT1-antagonist activity of the substances under study by the change of retractive activity of the vessels in comparison with angiotensin II effect (Δ%). Statistic processing of the results of the study was carried out in GraphPad Prism 6.9 program with the use of Mann-Whitney test. Results: we have studied AT1-blocking activity of 15 new biphenyl-bearing derivatives of benzimidazole, synthesized by a scientific worker at the Scientific and Research Institute of Physical and Organic Chemistry of Southern Federal University Ph.D. in Chemistry O.N. Zhukovsky. As the result of the test of the compounds of this variety we did not encountered a significant AT1-antagonist effect. At that, the highest level of activity, exhibited by the substance with AJ-146 code, amounted to -28.6±14.1Δ%. Valsartan comparative drug exhibited a signified AT1-blocking action at dose 10 µmol/l -98,3±0,7Δ%. Conclusions: thus, we have established that there were no compounds with signified AT1-antagonist effect in the variety of new benzimidazole derivatives and biphenyl.