2H-1,4-Benzoxazin-3(4H)-one linked 1,2,3-triazole derivatives and their study on inducing DNA damage in tumor cells
This study explores the anticancer potential of rigid planar compounds capable of intercalating into tumor cell DNA, thereby inducing DNA damage and subsequent cell death. A novel series of compounds (c1–c20) were synthesized using 2H-1,4-benzoxazin-3(4H)-one as the planar core structure, with 1,2,3...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1564090/full |
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| author | Xixi Hou Yajie Guo Xi Wang En Gao En Gao Jianxue Yang |
| author_facet | Xixi Hou Yajie Guo Xi Wang En Gao En Gao Jianxue Yang |
| author_sort | Xixi Hou |
| collection | DOAJ |
| description | This study explores the anticancer potential of rigid planar compounds capable of intercalating into tumor cell DNA, thereby inducing DNA damage and subsequent cell death. A novel series of compounds (c1–c20) were synthesized using 2H-1,4-benzoxazin-3(4H)-one as the planar core structure, with 1,2,3-triazole groups introduced at the 7-position. Biological evaluation across multiple human tumor cell lines revealed that several c-series compounds exhibited notable inhibitory activity against Huh-7 liver cancer cells, with IC50 values of 28.48 μM (c5), 32.60 μM (c14), 31.87 μM (c16), and 19.05 μM (c18). Mechanistic studies indicated that these compounds effectively induced DNA damage, as evidenced by the upregulation of γ-H2AX, and triggered apoptosis via increased caspase-7 expression. Moreover, enhanced LC3 expression and autophagosome formation suggested the activation of autophagy pathways. The observed biological activities are likely attributed to the rigid planar configuration of the molecules, which facilitates DNA intercalation. Collectively, these results highlight the potential of these synthesized compounds as promising lead candidates for the development of novel therapeutic agents against liver cancer. Importantly, acute toxicity studies in mice demonstrated that these compounds possess favorable safety profiles, further supporting their potential for future preclinical development. |
| format | Article |
| id | doaj-art-e0300a740d7a4693ace7e11c55d637b4 |
| institution | DOAJ |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-e0300a740d7a4693ace7e11c55d637b42025-08-20T03:03:16ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-08-011610.3389/fphar.2025.156409015640902H-1,4-Benzoxazin-3(4H)-one linked 1,2,3-triazole derivatives and their study on inducing DNA damage in tumor cellsXixi Hou0Yajie Guo1Xi Wang2En Gao3En Gao4Jianxue Yang5The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, ChinaDepartment of Emergency, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, ChinaSchool of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, ChinaSchool of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, ChinaState Key Laboratory of Quality Research in Chinese Medicine/Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, ChinaThe First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, ChinaThis study explores the anticancer potential of rigid planar compounds capable of intercalating into tumor cell DNA, thereby inducing DNA damage and subsequent cell death. A novel series of compounds (c1–c20) were synthesized using 2H-1,4-benzoxazin-3(4H)-one as the planar core structure, with 1,2,3-triazole groups introduced at the 7-position. Biological evaluation across multiple human tumor cell lines revealed that several c-series compounds exhibited notable inhibitory activity against Huh-7 liver cancer cells, with IC50 values of 28.48 μM (c5), 32.60 μM (c14), 31.87 μM (c16), and 19.05 μM (c18). Mechanistic studies indicated that these compounds effectively induced DNA damage, as evidenced by the upregulation of γ-H2AX, and triggered apoptosis via increased caspase-7 expression. Moreover, enhanced LC3 expression and autophagosome formation suggested the activation of autophagy pathways. The observed biological activities are likely attributed to the rigid planar configuration of the molecules, which facilitates DNA intercalation. Collectively, these results highlight the potential of these synthesized compounds as promising lead candidates for the development of novel therapeutic agents against liver cancer. Importantly, acute toxicity studies in mice demonstrated that these compounds possess favorable safety profiles, further supporting their potential for future preclinical development.https://www.frontiersin.org/articles/10.3389/fphar.2025.1564090/full2H-14-benzoxazin-3(4H)-one1,2,3-triazoleanti-tumor DNA damageapoptosis |
| spellingShingle | Xixi Hou Yajie Guo Xi Wang En Gao En Gao Jianxue Yang 2H-1,4-Benzoxazin-3(4H)-one linked 1,2,3-triazole derivatives and their study on inducing DNA damage in tumor cells Frontiers in Pharmacology 2H-1 4-benzoxazin-3(4H)-one 1,2,3-triazole anti-tumor DNA damage apoptosis |
| title | 2H-1,4-Benzoxazin-3(4H)-one linked 1,2,3-triazole derivatives and their study on inducing DNA damage in tumor cells |
| title_full | 2H-1,4-Benzoxazin-3(4H)-one linked 1,2,3-triazole derivatives and their study on inducing DNA damage in tumor cells |
| title_fullStr | 2H-1,4-Benzoxazin-3(4H)-one linked 1,2,3-triazole derivatives and their study on inducing DNA damage in tumor cells |
| title_full_unstemmed | 2H-1,4-Benzoxazin-3(4H)-one linked 1,2,3-triazole derivatives and their study on inducing DNA damage in tumor cells |
| title_short | 2H-1,4-Benzoxazin-3(4H)-one linked 1,2,3-triazole derivatives and their study on inducing DNA damage in tumor cells |
| title_sort | 2h 1 4 benzoxazin 3 4h one linked 1 2 3 triazole derivatives and their study on inducing dna damage in tumor cells |
| topic | 2H-1 4-benzoxazin-3(4H)-one 1,2,3-triazole anti-tumor DNA damage apoptosis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1564090/full |
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