Synthesis, telomerase inhibitory and anticancer activity of new 2-phenyl-4H-chromone derivatives containing 1,3,4-oxadiazole moiety
Based on previous studies, 66 2-phenyl-4H-chromone derivatives containing amide and 1,3,4-oxadiazole moieties were prepared as potential telomerase inhibitors. The results showed most of the title compounds exhibited significantly inhibitory activity on telomerase. Among them, some compounds demonst...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | http://dx.doi.org/10.1080/14756366.2020.1864630 |
| _version_ | 1818332571692433408 |
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| author | Xu Han Yun Long Yu Duo Ma Zhao Yan Zhang Xin Hua Liu |
| author_facet | Xu Han Yun Long Yu Duo Ma Zhao Yan Zhang Xin Hua Liu |
| author_sort | Xu Han |
| collection | DOAJ |
| description | Based on previous studies, 66 2-phenyl-4H-chromone derivatives containing amide and 1,3,4-oxadiazole moieties were prepared as potential telomerase inhibitors. The results showed most of the title compounds exhibited significantly inhibitory activity on telomerase. Among them, some compounds demonstrated the most potent telomerase inhibitory activity (IC50 < 1 µM), which was significantly superior to the staurosporine (IC50 = 6.41 µM). In addition, clear structure–activity relationships were summarised, indicating that the substitution of the methoxy group and the position, type and number of the substituents on the phenyl ring had significant effects on telomerase activity. Among them, compound A33 showed considerable inhibition against telomerase. Flow cytometric analysis showed that compound A33 could arrest MGC-803 cell cycle at G2/M phase and induce apoptosis in a concentration-dependent way. Meanwhile, Western blotting revealed that this compound could reduce the expression of dyskerin, which is a fragment of telomerase. |
| first_indexed | 2024-12-13T13:37:52Z |
| format | Article |
| id | doaj.art-7b4619047aa046dda50e031ee8716e87 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-12-13T13:37:52Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-7b4619047aa046dda50e031ee8716e872022-12-21T23:43:41ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742021-01-0136134536110.1080/14756366.2020.18646301864630Synthesis, telomerase inhibitory and anticancer activity of new 2-phenyl-4H-chromone derivatives containing 1,3,4-oxadiazole moietyXu Han0Yun Long Yu1Duo Ma2Zhao Yan Zhang3Xin Hua Liu4School of Pharmacy, Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical UniversitySchool of Pharmacy, Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical UniversitySchool of Pharmacy, Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical UniversitySchool of Pharmacy, Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical UniversitySchool of Pharmacy, Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical UniversityBased on previous studies, 66 2-phenyl-4H-chromone derivatives containing amide and 1,3,4-oxadiazole moieties were prepared as potential telomerase inhibitors. The results showed most of the title compounds exhibited significantly inhibitory activity on telomerase. Among them, some compounds demonstrated the most potent telomerase inhibitory activity (IC50 < 1 µM), which was significantly superior to the staurosporine (IC50 = 6.41 µM). In addition, clear structure–activity relationships were summarised, indicating that the substitution of the methoxy group and the position, type and number of the substituents on the phenyl ring had significant effects on telomerase activity. Among them, compound A33 showed considerable inhibition against telomerase. Flow cytometric analysis showed that compound A33 could arrest MGC-803 cell cycle at G2/M phase and induce apoptosis in a concentration-dependent way. Meanwhile, Western blotting revealed that this compound could reduce the expression of dyskerin, which is a fragment of telomerase.http://dx.doi.org/10.1080/14756366.2020.18646302-phenyl-4h-chromonesynthesistelomerase inhibitoranticancer activitydyskerin |
| spellingShingle | Xu Han Yun Long Yu Duo Ma Zhao Yan Zhang Xin Hua Liu Synthesis, telomerase inhibitory and anticancer activity of new 2-phenyl-4H-chromone derivatives containing 1,3,4-oxadiazole moiety Journal of Enzyme Inhibition and Medicinal Chemistry 2-phenyl-4h-chromone synthesis telomerase inhibitor anticancer activity dyskerin |
| title | Synthesis, telomerase inhibitory and anticancer activity of new 2-phenyl-4H-chromone derivatives containing 1,3,4-oxadiazole moiety |
| title_full | Synthesis, telomerase inhibitory and anticancer activity of new 2-phenyl-4H-chromone derivatives containing 1,3,4-oxadiazole moiety |
| title_fullStr | Synthesis, telomerase inhibitory and anticancer activity of new 2-phenyl-4H-chromone derivatives containing 1,3,4-oxadiazole moiety |
| title_full_unstemmed | Synthesis, telomerase inhibitory and anticancer activity of new 2-phenyl-4H-chromone derivatives containing 1,3,4-oxadiazole moiety |
| title_short | Synthesis, telomerase inhibitory and anticancer activity of new 2-phenyl-4H-chromone derivatives containing 1,3,4-oxadiazole moiety |
| title_sort | synthesis telomerase inhibitory and anticancer activity of new 2 phenyl 4h chromone derivatives containing 1 3 4 oxadiazole moiety |
| topic | 2-phenyl-4h-chromone synthesis telomerase inhibitor anticancer activity dyskerin |
| url | http://dx.doi.org/10.1080/14756366.2020.1864630 |
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