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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引用次数: 0
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.
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.