Cytoprotective Activity of Newly Synthesized 3-(Arylmethylamino)-6-Methyl-4-Phenylpyridin-2(1)-Ones Derivatives

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2022 Sep 9

PMID 36080132

Authors

Shynggys Sergazy

Zarina Shulgau

Aigerim Zhulikeyeva

Yerlan Ramankulov

Irina V Palamarchuk

Ivan V Kulakov

Affiliations

Soon will be listed here.

Abstract

Currently, studies are being conducted on the possible role of the cytoprotective effect of biologically active substances in conditions of cerebral hypoxia or cardiomyopathies. At the same time, oxidative stress is considered one of the important mechanisms of cellular cytotoxicity and a target for the action of cytoprotectors. The aim of this study is to search for derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1)-ones. The probability of cytoprotective action was assessed by measuring cell viability using two tests (with neutral red dye and MTT test). It was found that some derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1)-ones under the conditions of our experiment had a pronounced cytoprotective activity, providing better cell survival in vitro, including the MTT test and conditions of blood hyperviscosity. To correlate the obtained results in vitro, molecular docking of the synthesized derivatives was also carried out. The standard drug omeprazole (co-crystallized with the enzyme) was used as a standard. It was shown that all synthesized derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1)-ones had higher affinity for the selected protein than the standard gastro-cytoprotector omeprazole. The studied derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1)-ones also fully satisfy Lipinski's rule of five (RO5), which increases their chances for possible use as orally active drugs with good absorption ability and moderate lipophilicity. Thus, the results obtained make it possible to evaluate derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1)-ones as having a relatively high cytoprotective potential.

Citing Articles

Synthesis, Computational Study, and In Vitro α-Glucosidase Inhibitory Action of Thiourea Derivatives Based on 3-Aminopyridin-2(1)-Ones.

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