ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1564090
2H-1,4-Benzoxazin-3(4H)-one Linked 1,2,3-Triazole Derivatives and Their Study on Inducing DNA Damage in Tumor Cells
Provisionally accepted
- 1The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
- 2The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
- 3Henan University of Science and Technology, Luoyang, China
- 4Henan Normal University, Xinxiang, Henan Province, China
- 5The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan Province, China
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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) was 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.
Keywords: 2H-1, 4-benzoxazin-3(4H)-one, 1, 2, 3-triazole, anti-tumor DNA damage, Apoptosis
Received: 21 Jan 2025; Accepted: 08 Jul 2025.
Copyright: © 2025 Hou, Guo, Mao, Gao, Yang and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yajie Guo, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518033, China
Longfei Mao, Henan University of Science and Technology, Luoyang, China
Jianxue Yang, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan Province, China
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