A Hypoxia-Activated BODIPY-Azo Anticancer Prodrug for Bimodal Chemo-Photodynamic Therapy

IF 6.8 1区 医学 Q1 CHEMISTRY, MEDICINAL Journal of Medicinal Chemistry Pub Date : 2025-01-18 DOI:10.1021/acs.jmedchem.4c02231
Ting Zhang, Baoyin Yang, Tao Jiang, Xiangyu Kong, Xinyao Huo, Yan Ma, Kehao Yang, Mengchun Liu, Yumiao Liu, Zikuo Yao, Hao Yu, Huining Liu, Kai Zhang, Yifan Liu
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Abstract

For cancer treatment, collaborative strategies have been the mainstream for overcoming the restrictions resulting from monotherapy. Combining chemotherapy with photodynamic therapy (PDT) has been shown to increase the antitumor effect and reduce side impacts. This study reports a hypoxia-activated prodrug BOD-Azo-single with a PDT agent and aniline mustard connected by the azo bond. With light illumination, BOD-Azo-single exhibited some PDT. Under hypoxic conditions, the azo bond cleaved and released BOD-3-single of higher phototoxicity and aniline mustard of chemotoxicity. In vivo therapeutic experiments showed that BOD-Azo-single with light significantly reduced A375 tumor proliferation with 92% TGI value. Overall, in this study, PDT was employed to address the adverse systemic toxicity of chemotherapy and the released chemotoxicity made up for the inefficiency of PDT in the hypoxic tumor microenvironment, introducing a new strategy for developing combined therapeutic agents to be advantageous to each other. Under a hypoxic tumor environment, BOD-3-single and aniline mustard exerted a strong synergistic effect (CI = 0.25), indicating that BOD-Azo-single is a real bimodal chemo-photodynamic therapeutic agent.

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一种用于双峰化学光动力治疗的低氧活化体-偶氮抗癌前药
对于癌症治疗,协作策略已经成为克服单一疗法限制的主流。化疗联合光动力疗法(PDT)已被证明可以提高抗肿瘤效果,减少副作用。本研究报道了一种缺氧激活的前药bod -偶氮单药,其中PDT剂和苯胺芥菜通过偶氮键连接。在光照条件下,BOD-Azo-single表现出一定的PDT。在缺氧条件下,偶氮键断裂,释放出具有较高光毒性的bod -3单链和具有化学毒性的苯胺芥菜。体内治疗实验表明,BOD-Azo-single在光照下显著降低A375肿瘤的增殖,TGI值达到92%。综上所述,本研究利用PDT来解决化疗的不良全身毒性,释放的化学毒性弥补了PDT在缺氧肿瘤微环境中的无效,为开发相互有利的联合治疗药物提供了新的策略。在低氧肿瘤环境下,BOD-3-single与苯胺芥菜具有较强的协同作用(CI = 0.25),表明BOD-Azo-single是一种真正的双峰化学光动力治疗剂。
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来源期刊
Journal of Medicinal Chemistry
Journal of Medicinal Chemistry 医学-医药化学
CiteScore
4.00
自引率
11.00%
发文量
804
审稿时长
1.9 months
期刊介绍: The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents. The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.
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