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目的 合成基于吩噻嗪结构的喹啉盐光敏剂(PATTQ)，系统探究其光物理性质及体外抗肿瘤活性，为新型光敏剂的研发提供实验依据。方法 采用钯催化直接芳基化、Knoevenagel 缩合及阳离子化反应，合成具有D-π-A结构的新型有机Ⅰ/Ⅱ型光敏剂PATTQ；运用核磁共振氢谱(~~1H NMR)、碳谱~((~)(13)C NMR)及质谱(MS)确证其化学结构；通过密度泛函理论(DFT)计算分析PATTQ的电子行为及系间窜越过程；利用紫外-可见吸收光谱、荧光光谱考察其光物理性质；分别采用ABDA、DHR123、HPF探针法评估PATTQ产生单~线态_氧(~1O2)、超氧阴离_子自由基(O2·~-)、羟基自由基(·OH)的能力；通过CCK-8法检测其对人乳腺癌MCF-7细胞的体外抗~肿瘤活性。结果 ~1H NMR、13C NMR及MS数据证实PATTQ化学结构正确；DFT计算显示，PATTQ的单重态-三重态能级差■为0.021 eV，表明分子可能发生S_n_→Tn态系间窜越，为活性氧(ROS)生成提供有利条件；ABDA探针检测结果显示，PAT~TQ_的~1O2生成能力优于市售光敏剂孟加拉玫瑰红(RB)，略低于市售光敏剂二氢卟吩e6(Ce6)；CCK-8实验表明，光照条件下PATTQ对MCF-7细胞增殖具有显著抑制作用。结论 成功合成基于吩噻嗪的喹啉盐光敏剂PATTQ，该光敏剂兼具Ⅰ/Ⅱ型光敏剂特性，且体外抗肿瘤活性显著，有望成为光动力治疗领域的潜在候选药物。
Abstract：Objective To synthesize a quinolinium salt photosensitizer (PATTQ) based on a phenothiazine structure,determine its photophysical properties and in vitro antitumor activity,and provide an experimental basis for developing novel photosensitizers.Methods A new organic photosensitizer,PATTQ,featuring a D-π-A structure and type Ⅰ/Ⅱ mechanisms,was synthesized through palladium-catalyzed direct arylation,Knoevenagel condensation,and cationization reactions.Its chemical structure was characterized with ~1H NMR,13C NMR,and mass spectrometry (MS).Density functional theory (DFT) helped analyze its electronic behavior and intersystem crossing process.The photophysical properties were examined with UV-visible absorption and fluorescence spectroscopy.The generation of singlet oxygen (~1O2),superoxide anion radical (O2·-),and hydroxyl radical (·OH) was assessed with ABDA,DHR123,and HPF probes,respectively.The in vitro antitumor activity against human breast cancer MCF-7 cells was evaluated with CCK-8 assay.Results Structural characterization by ~1H NMR,13C NMR,and MS confirmed the successful synthesis of PATTQ.DFT revealed a small singlet-triplet energy gap■of 0.021 eV,suggesting efficient Sn→Tn intersystem crossing conducive to the generation of reactive oxygen species (ROS).The ABDA probe assay indicated that the singlet oxygen generation capability of PATTQ was superior to that of the commercial photosensitizer Rose Bengal (RB)but slightly lower than that of chlorin e6 (Ce6).The CCK-8 assay showed that PATTQ greatly inhibited the proliferation of MCF-7 cells upon light irradiation.Conclusion The phenothiazine-based quinolinium salt photosensitizer PATTQ is successfully synthesized.It exhibits dual type Ⅰ/Ⅱ photosensitizing characteristics and demonstrates obvious in vitro antitumor activity,suggesting its potential as a candidate for photodynamic therapy.
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基本信息:
中图分类号:R914;R96
引用信息:
[1]王敬威,王棚,关静.具有吩噻嗪和喹啉结构的小分子光敏剂合成及体外抗肿瘤活性研究[J].中南药学,2026,24(03):14-21.
基金信息:
国家自然科学基金项目(No.81601542); 哈尔滨医科大学药学院优秀青年人才资助项目(No.2019-YQ-05); 黑龙江省博士后科研启动基金项目(No.LBHQ21125)
2026-03-19
2026-03-19