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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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Autores principales: Han, Xu, Yu, Yun Long, Ma, Duo, Zhang, Zhao Yan, Liu, Xin Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782168/
https://www.ncbi.nlm.nih.gov/pubmed/33356666
http://dx.doi.org/10.1080/14756366.2020.1864630
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author Han, Xu
Yu, Yun Long
Ma, Duo
Zhang, Zhao Yan
Liu, Xin Hua
author_facet Han, Xu
Yu, Yun Long
Ma, Duo
Zhang, Zhao Yan
Liu, Xin Hua
author_sort Han, Xu
collection PubMed
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 (IC(50) < 1 µM), which was significantly superior to the staurosporine (IC(50) = 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.
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spelling pubmed-77821682021-01-14 Synthesis, telomerase inhibitory and anticancer activity of new 2-phenyl-4H-chromone derivatives containing 1,3,4-oxadiazole moiety Han, Xu Yu, Yun Long Ma, Duo Zhang, Zhao Yan Liu, Xin Hua J Enzyme Inhib Med Chem Brief Report 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 (IC(50) < 1 µM), which was significantly superior to the staurosporine (IC(50) = 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. Taylor & Francis 2020-12-27 /pmc/articles/PMC7782168/ /pubmed/33356666 http://dx.doi.org/10.1080/14756366.2020.1864630 Text en © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Brief Report
Han, Xu
Yu, Yun Long
Ma, Duo
Zhang, Zhao Yan
Liu, Xin Hua
Synthesis, telomerase inhibitory and anticancer activity of new 2-phenyl-4H-chromone derivatives containing 1,3,4-oxadiazole moiety
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 Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782168/
https://www.ncbi.nlm.nih.gov/pubmed/33356666
http://dx.doi.org/10.1080/14756366.2020.1864630
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