The use of the docking studies with the purpose of searching potential cardioprotectors

personАвтори: I. Drapak, I. Sych, L. Perekhoda, M. Protopopov, M. Suleiman, N. Kobzar, O. Kiz, O. Vynogradova

Abstract: This work is one of the stages of searching for effective cardioprotectors of the metabolic action based on derivatives of 2-imino-1,3-thiazoline and 1,3,4-thiadiazole. Our study gives possibility to save laboratory animals and time, to carry out purposeful and effective research in future.

The receptor-based flexible docking of 154 compounds synthesized among 2-imino-1,3-thiazoline derivatives, which contain hydroxyethyl, methylpiperazine, morpholine, propylmorpholine, ethylmorpholine, ethyl fragments in the structure, and 2,5-disubstituted derivatives of 1,3,4-thiadiazole to the active site of gamma-butyrobetaine hydroxylase (IUBMB Enzyme Nomenclature: has been conducted with the purpose of directed search for inhibitors of this enzyme as potential cardio protectors of the metabolic action.

According to the docking results, 15 studied derivatives of 2-imino-1,3-thiazoline, which contain in the structure the morpholine and propyl morpholine fragment, and 3 derivatives of2-R,5-R-amine-1,3,4-thiadiazole,have values of affinity to the enzyme, which are comparable with the values of the classical inhibitors L-carnitine and reference drug mildronate. It is the argument for the study of the metabolic action of the 18 compounds under research in vivo. It should also be noted that compounds 8, 9 and 18 are the most promising according to the results of in silico studies. Вesides, 2-imino-1,3-thiazoline derivatives containing the morpholine and propyl morpholine fragment in the structure and derivatives of 2-R,5-R-amine-1,3,4-thiadiazole can be regarded as a promising scaffolds for creating combinatorial libraries of potential cardio protectors of the metabolic action.

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