Wang Zihao, Liu Xiao, Ma Yifan, Zheng Jiaxin, Xu Ke, Chang Yingxue, Ye Zhaoyan, Ling Yong, Wang Lei
Department of Medicinal Chemistry, School of Pharmacy, Nantong University, Nantong 226001, China.
Department of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
Molecules. 2025 Jun 12;30(12):2560. doi: 10.3390/molecules30122560.
To address the clinical challenges posed by symbiotic drug-resistant bacterial infections and tumor microenvironments, this study designed and synthesized novel carbazole/benzindole-based photosensitizers -, systematically evaluating their antitumor and antibacterial therapeutic potential through chemo-photodynamic therapy. Especially, compound demonstrated potent Type I/II reactive oxygen species (ROS) generation capabilities. In vitro experiments revealed that concentration-dependently inhibited HT-29 cells under hypoxic conditions (IC = 0.89 μM) with a prominent photodynamic index (PI > 9.23), and substantially promoted cancer cell programmed death. In antibacterial evaluations, achieved the complete eradication of dermal MRSA infections within 7 days through ROS-mediated membrane disruption under illumination. In the HT-29 xenograft model, the PDT-chemotherapy synergy strategy achieved a tumor suppression rate of 96%. This work establishes an innovative strategy for the combinatorial management of multidrug-resistant infections and solid tumors.
为应对共生性耐药细菌感染和肿瘤微环境带来的临床挑战，本研究设计并合成了新型咔唑/苯并吲哚基光敏剂，通过化学光动力疗法系统评估其抗肿瘤和抗菌治疗潜力。特别是，化合物表现出强大的I/II型活性氧（ROS）生成能力。体外实验表明，在缺氧条件下，该化合物浓度依赖性地抑制HT-29细胞（IC = 0.89 μM），具有显著的光动力指数（PI > 9.23），并大幅促进癌细胞程序性死亡。在抗菌评估中，该化合物通过光照下ROS介导的膜破坏在7天内实现了对皮肤耐甲氧西林金黄色葡萄球菌感染的完全根除。在HT-29异种移植模型中，光动力疗法-化疗协同策略实现了96%的肿瘤抑制率。这项工作为多重耐药感染和实体瘤的联合管理建立了一种创新策略。
