Cytoprotective Activity of Newly Synthesized 3-(Arylmethylamino)-6-Methyl-4-Phenylpyridin-2(1<i>H</i>)-Ones Derivatives
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...
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MDPI AG
2022-08-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/17/5362 |
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| author | Shynggys Sergazy Zarina Shulgau Aigerim Zhulikeyeva Yerlan Ramankulov Irina V. Palamarchuk Ivan V. Kulakov |
| author_facet | Shynggys Sergazy Zarina Shulgau Aigerim Zhulikeyeva Yerlan Ramankulov Irina V. Palamarchuk Ivan V. Kulakov |
| author_sort | Shynggys Sergazy |
| collection | DOAJ |
| description | 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<i>H</i>)-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<i>H</i>)-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<i>H</i>)-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<i>H</i>)-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<i>H</i>)-ones as having a relatively high cytoprotective potential. |
| first_indexed | 2024-03-10T01:31:55Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T01:31:55Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-b6f8e2c3726a4c3bb5e0092cff4a7f3b2023-11-23T13:40:43ZengMDPI AGMolecules1420-30492022-08-012717536210.3390/molecules27175362Cytoprotective Activity of Newly Synthesized 3-(Arylmethylamino)-6-Methyl-4-Phenylpyridin-2(1<i>H</i>)-Ones DerivativesShynggys Sergazy0Zarina Shulgau1Aigerim Zhulikeyeva2Yerlan Ramankulov3Irina V. Palamarchuk4Ivan V. Kulakov5RSE “National Center for Biotechnology”, 13/5 Kurgalzhynskoe Road, Nur-Sultan 010000, KazakhstanRSE “National Center for Biotechnology”, 13/5 Kurgalzhynskoe Road, Nur-Sultan 010000, KazakhstanRSE “National Center for Biotechnology”, 13/5 Kurgalzhynskoe Road, Nur-Sultan 010000, KazakhstanRSE “National Center for Biotechnology”, 13/5 Kurgalzhynskoe Road, Nur-Sultan 010000, KazakhstanInstitute of Chemistry, Tyumen State University, 15a Perekopskaya St., 625003 Tyumen, RussiaRSE “National Center for Biotechnology”, 13/5 Kurgalzhynskoe Road, Nur-Sultan 010000, KazakhstanCurrently, 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<i>H</i>)-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<i>H</i>)-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<i>H</i>)-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<i>H</i>)-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<i>H</i>)-ones as having a relatively high cytoprotective potential.https://www.mdpi.com/1420-3049/27/17/53623-aminopyridin-2(1<i>H</i>)-one derivatives3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1<i>H</i>)-onesantiradical activitycytoprotective activity |
| spellingShingle | Shynggys Sergazy Zarina Shulgau Aigerim Zhulikeyeva Yerlan Ramankulov Irina V. Palamarchuk Ivan V. Kulakov Cytoprotective Activity of Newly Synthesized 3-(Arylmethylamino)-6-Methyl-4-Phenylpyridin-2(1<i>H</i>)-Ones Derivatives Molecules 3-aminopyridin-2(1<i>H</i>)-one derivatives 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1<i>H</i>)-ones antiradical activity cytoprotective activity |
| title | Cytoprotective Activity of Newly Synthesized 3-(Arylmethylamino)-6-Methyl-4-Phenylpyridin-2(1<i>H</i>)-Ones Derivatives |
| title_full | Cytoprotective Activity of Newly Synthesized 3-(Arylmethylamino)-6-Methyl-4-Phenylpyridin-2(1<i>H</i>)-Ones Derivatives |
| title_fullStr | Cytoprotective Activity of Newly Synthesized 3-(Arylmethylamino)-6-Methyl-4-Phenylpyridin-2(1<i>H</i>)-Ones Derivatives |
| title_full_unstemmed | Cytoprotective Activity of Newly Synthesized 3-(Arylmethylamino)-6-Methyl-4-Phenylpyridin-2(1<i>H</i>)-Ones Derivatives |
| title_short | Cytoprotective Activity of Newly Synthesized 3-(Arylmethylamino)-6-Methyl-4-Phenylpyridin-2(1<i>H</i>)-Ones Derivatives |
| title_sort | cytoprotective activity of newly synthesized 3 arylmethylamino 6 methyl 4 phenylpyridin 2 1 i h i ones derivatives |
| topic | 3-aminopyridin-2(1<i>H</i>)-one derivatives 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1<i>H</i>)-ones antiradical activity cytoprotective activity |
| url | https://www.mdpi.com/1420-3049/27/17/5362 |
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