Redox-Inactive Terpyridine Zn(II)-Azide Complexes for Photodynamic and Photoactivatable Chemotherapy.

IF 6.8 1区医学 Q1 CHEMISTRY, MEDICINAL

Journal of Medicinal Chemistry Pub Date : 2025-09-29 DOI:10.1021/acs.jmedchem.5c01612

Tejal Dixit,Kartikay Tyagi,V Venkatesh

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引用次数: 0

Abstract

The rational design of metal complexes exhibiting both photodynamic therapy (PDT) and photoactivatable chemotherapy (PACT) remains a significant challenge in the phototherapeutic regimen. Herein, we developed a series of terpyridine zinc(II)-azide complexes; among them, lead complex Tpatpy@ZnN3 shows both type I and type II PDT, along with the photorelease of azidyl radicals. The Tpatpy@ZnN3 complex targets mitochondria; upon blue light activation (456 nm), it generates singlet oxygen (1O2), hydroxyl radical (•OH), and azidyl radical (N3•). The produced reactive oxygen and nitrogen species induce oxidative stress, ultimately leading to mitochondrial-mediated cellular apoptosis. The complex demonstrated significant efficacy in both two-dimensional (2D) cancer cells and three-dimensional (3D) multicellular tumor spheroids. Notably, the zinc(II) complex is biocompatible, cost-effective, and redox-inactive, exhibiting negligible dark toxicity. This study highlights the efficacy of Tpatpy@ZnN3 for synergistic and enhanced therapeutic potential with spatial and temporal precision, paving the way for the development of photoactivatable zinc complexes for cancer therapy.

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用于光动力和光活化化疗的氧化还原活性三联吡啶锌（II）叠氮化物配合物。

在光疗方案中，合理设计具有光动力治疗（PDT）和光活化化疗（PACT）功能的金属配合物仍然是一个重大挑战。在此，我们开发了一系列的三吡啶锌（II）叠氮化物配合物；其中，铅配合物Tpatpy@ZnN3同时表现出I型和II型PDT，并伴有叠氮基自由基的光释放。Tpatpy@ZnN3复合物以线粒体为目标；在蓝光激活（456nm）时，产生单线态氧（1O2）、羟基自由基（•OH）和叠氮基自由基（N3•）。产生的活性氧和活性氮诱导氧化应激，最终导致线粒体介导的细胞凋亡。该复合物对二维（2D）癌细胞和三维（3D）多细胞肿瘤球体均有显著疗效。值得注意的是，锌（II）配合物具有生物相容性、成本效益和氧化还原活性，表现出可忽略不计的暗毒性。该研究强调了Tpatpy@ZnN3在空间和时间精度上的协同和增强治疗潜力的功效，为开发用于癌症治疗的光活化锌复合物铺平了道路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

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.