Synthesis of Novel 2-(Pyridin-2-yl) Pyrimidine Derivatives and Study of Their Anti-Fibrosis Activity
A pyrimidine moiety exhibiting a wide range of pharmacological activities has been employed in the design of privileged structures in medicinal chemistry. To prepare libraries of novel heterocyclic compounds with potential biological activities, a series of novel 2-(pyridin-2-yl) pyrimidine derivati...
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| Format: | Article |
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MDPI AG
2020-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/22/5226 |
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| author | Yi-Fei Gu Yue Zhang Feng-li Yue Shao-tong Li Zhuo-qi Zhang Jing Li Xu Bai |
| author_facet | Yi-Fei Gu Yue Zhang Feng-li Yue Shao-tong Li Zhuo-qi Zhang Jing Li Xu Bai |
| author_sort | Yi-Fei Gu |
| collection | DOAJ |
| description | A pyrimidine moiety exhibiting a wide range of pharmacological activities has been employed in the design of privileged structures in medicinal chemistry. To prepare libraries of novel heterocyclic compounds with potential biological activities, a series of novel 2-(pyridin-2-yl) pyrimidine derivatives were designed, synthesized and their biological activities were evaluated against immortalized rat hepatic stellate cells (HSC-T6). Fourteen compounds were found to present better anti-fibrotic activities than Pirfenidone and Bipy55′DC. Among them, compounds ethyl 6-(5-(<i>p</i>-tolylcarbamoyl)pyrimidin-2-yl)nicotinate (<b>12m</b>) and ethyl 6-(5-((3,4-difluorophenyl)carbamoyl)pyrimidin-2-yl)nicotinate (<b>12q</b>) show the best activities with IC<sub>50</sub> values of 45.69 μM and 45.81 μM, respectively. Furthermore, the study of anti-fibrosis activity was evaluated by Picro-Sirius red staining, hydroxyproline assay and ELISA detection of Collagen type I alpha 1 (COL1A1) protein expression. Our study showed that compounds <b>12m</b> and <b>12q</b> effectively inhibited the expression of collagen, and the content of hydroxyproline in cell culture medium in vitro, indicating that compounds <b>12m</b> and <b>12q</b> might be developed the novel anti-fibrotic drugs. |
| first_indexed | 2024-03-10T14:59:11Z |
| format | Article |
| id | doaj.art-c1a12b8ff45c43338171557fc6176116 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T14:59:11Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-c1a12b8ff45c43338171557fc61761162023-11-20T20:23:12ZengMDPI AGMolecules1420-30492020-11-012522522610.3390/molecules25225226Synthesis of Novel 2-(Pyridin-2-yl) Pyrimidine Derivatives and Study of Their Anti-Fibrosis ActivityYi-Fei Gu0Yue Zhang1Feng-li Yue2Shao-tong Li3Zhuo-qi Zhang4Jing Li5Xu Bai6The Center for Combinatorial Chemistry and Drug Discovery of Jilin University, The School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun 130021, ChinaThe Center for Combinatorial Chemistry and Drug Discovery of Jilin University, The School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun 130021, ChinaDepartment of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaDepartment of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaThe Center for Combinatorial Chemistry and Drug Discovery of Jilin University, The School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun 130021, ChinaDepartment of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaThe Center for Combinatorial Chemistry and Drug Discovery of Jilin University, The School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun 130021, ChinaA pyrimidine moiety exhibiting a wide range of pharmacological activities has been employed in the design of privileged structures in medicinal chemistry. To prepare libraries of novel heterocyclic compounds with potential biological activities, a series of novel 2-(pyridin-2-yl) pyrimidine derivatives were designed, synthesized and their biological activities were evaluated against immortalized rat hepatic stellate cells (HSC-T6). Fourteen compounds were found to present better anti-fibrotic activities than Pirfenidone and Bipy55′DC. Among them, compounds ethyl 6-(5-(<i>p</i>-tolylcarbamoyl)pyrimidin-2-yl)nicotinate (<b>12m</b>) and ethyl 6-(5-((3,4-difluorophenyl)carbamoyl)pyrimidin-2-yl)nicotinate (<b>12q</b>) show the best activities with IC<sub>50</sub> values of 45.69 μM and 45.81 μM, respectively. Furthermore, the study of anti-fibrosis activity was evaluated by Picro-Sirius red staining, hydroxyproline assay and ELISA detection of Collagen type I alpha 1 (COL1A1) protein expression. Our study showed that compounds <b>12m</b> and <b>12q</b> effectively inhibited the expression of collagen, and the content of hydroxyproline in cell culture medium in vitro, indicating that compounds <b>12m</b> and <b>12q</b> might be developed the novel anti-fibrotic drugs.https://www.mdpi.com/1420-3049/25/22/5226anti-fibrosiscollagen prolyl 4-hydroxylasespyrimidineCOL1A1synthesis |
| spellingShingle | Yi-Fei Gu Yue Zhang Feng-li Yue Shao-tong Li Zhuo-qi Zhang Jing Li Xu Bai Synthesis of Novel 2-(Pyridin-2-yl) Pyrimidine Derivatives and Study of Their Anti-Fibrosis Activity Molecules anti-fibrosis collagen prolyl 4-hydroxylases pyrimidine COL1A1 synthesis |
| title | Synthesis of Novel 2-(Pyridin-2-yl) Pyrimidine Derivatives and Study of Their Anti-Fibrosis Activity |
| title_full | Synthesis of Novel 2-(Pyridin-2-yl) Pyrimidine Derivatives and Study of Their Anti-Fibrosis Activity |
| title_fullStr | Synthesis of Novel 2-(Pyridin-2-yl) Pyrimidine Derivatives and Study of Their Anti-Fibrosis Activity |
| title_full_unstemmed | Synthesis of Novel 2-(Pyridin-2-yl) Pyrimidine Derivatives and Study of Their Anti-Fibrosis Activity |
| title_short | Synthesis of Novel 2-(Pyridin-2-yl) Pyrimidine Derivatives and Study of Their Anti-Fibrosis Activity |
| title_sort | synthesis of novel 2 pyridin 2 yl pyrimidine derivatives and study of their anti fibrosis activity |
| topic | anti-fibrosis collagen prolyl 4-hydroxylases pyrimidine COL1A1 synthesis |
| url | https://www.mdpi.com/1420-3049/25/22/5226 |
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