CYTOPROTECTIVE ACTIVITY OF NEWLY SYNTHESIZED 3-(ARYLMETHYLAMINO)-6-METHYL-4-PHENYLPYRIDIN-2(1H)-ONES DERIVATIVES
Date
2022-08-23
Authors
Sergazy, Shynggys
Shulgau, Zarina
Zhulikeyeva, Aigerim
Ramankulov, Yerlan
Palamarchuk, Irina V.
Kulakov, Ivan V.
Journal Title
Journal ISSN
Volume Title
Publisher
Molecules
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(1H)-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(1H)-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(1H)-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(1H)-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(1H)-ones as having a relatively high
cytoprotective potential.
Description
Keywords
Type of access: Open Access, 3-aminopyridin-2(1H)-one derivatives, 3-(arylmethylamino)-6-methyl-4-phenylpyridin2(1H)-ones, antiradical activity, cytoprotective activity
Citation
Sergazy, S., Shulgau, Z., Zhulikeyeva, A., Ramankulov, Y., Palamarchuk, I. V., & Kulakov, I. V. (2022). Cytoprotective Activity of Newly Synthesized 3-(Arylmethylamino)-6-Methyl-4-Phenylpyridin-2(1H)-Ones Derivatives. Molecules, 27(17), 5362. https://doi.org/10.3390/molecules27175362