The use of the docking studies with the purpose of searching potential antihypertensive drugs

Abstract

Pre-experimental studies in silico successfully used at various stages of the search and optimization of the structures of biologically active compounds. The purpose of present research was the search for perspective antihypertensive agents among 160 new ynthesized N-R-phenyl-2,3-dihydro-1,3-thiazole-2-imine derivatives containing the morpholine, ethyl(propyl)morpholine, hydroxyethyl, allyl moiety in the structure and 5- substituted derivatives of 2-thio(amino)-1,3,4-thiadiazole using docking studies to two biotargets of angiotensin converting enzyme and angiotensin II receptor. Based on the results of a flexible molecular docking, a promising group of N-R-phenyl-2,3-dihydro-1,3-thiazole-2-imine derivatives containing the morpholine moiety for experimental screening for antihypertensive activity was selected. The high affinity of this series of substances is associated with the formation of bonds between the Oxygen atom of the morpholine cycle and the corresponding amino acid residue in the active site of the angiotensin converting enzyme ІІ. According to data obtained, different lengths of alkyl chains between the Nitrogen atom of the morpholine cycle and the Nitrogen atom of 1,3-thiazole cycle of the test substances, have a significant impact on the general energy system of complexes formed during interaction of molecules of the substances under research and the enzyme specified.