| 倪礼礼,杜煜,姚佳,胡立中,张贺伟,王雪杨.化学通报,2026,89(5):545-556. |
| 喹诺酮杂化分子作为多靶点抗肿瘤药物的研究现状与展望 |
| Research progress and future perspectives of quinolone hybrid molecules as multi-target antitumor agents |
| 投稿时间：2025-12-29 修订日期：2026-03-25 |
| DOI： |
| 中文关键词: 喹诺酮杂化分子 多靶点抗肿瘤药物 分子杂交技术 构效关系 成药性 |
| 英文关键词:quinolone hybrid molecules multi-target antitumor molecular hybridization structure-activity relationship (SAR) druggability |
| 基金项目:河南省高等学校重点科研项目(25A230011)和河洛青年人才托举工程项目(2025HLTJ36)资助 |
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| 中文摘要: |
| 癌症的高发病率与多药耐药性使传统化疗药物疗效受限，开发多靶点抗肿瘤药物成为研究热点。喹诺酮类化合物因其独特的结构可修饰性和多靶点作用潜力，近年来在抗肿瘤药物研究中备受关注。本文系统综述喹诺酮与肉桂酸、查尔酮、姜黄素等活性药效团的杂化设计策略及构效关系，阐述喹诺酮杂化分子通过抑制拓扑异构酶、干预 PI3K/AKT/mTOR 信号通路、调控表观遗传等多靶点协同发挥的抗肿瘤作用机制，分析其在理化性质、代谢稳定性、体外ADME特性等方面的成药性特征及毒性风险。总结该类分子在细胞与动物模型中的抗肿瘤研究进展，指出其当前面临水溶性差、成药性数据不完善、临床转化范式缺失等研发障碍。最后展望 AI 理性设计、类器官模型、纳米递送系统等新技术在喹诺酮杂化分子研发中的应用方向，为喹诺酮杂化多靶点抗肿瘤药物的研发提供理论参考。 |
| 英文摘要: |
| The high prevalence of cancer and the rise of multidrug resistance have significantly undermined the effectiveness of conventional chemotherapeutic agents, thereby making the development of multi-target antitumor drugs a primary research focus. In recent years, quinolone compounds have attracted considerable attention in antitumor drug research due to their unique structural modifiability and inherent potential for multi-target interactions. This paper provides a systematic review of the hybrid design strategies and structure-activity relationships (SAR) of quinolones conjugated with bioactive pharmacophores, such as cinnamic acid, chalcones, and curcumin. It delves into the multi-target synergistic antitumor mechanisms of quinolone hybrid molecules, including topoisomerase inhibition, interference with the PI3K/AKT/mTOR signaling pathway, and epigenetic regulation. Furthermore, the study examines their druggability characteristics, encompassing physicochemical properties, metabolic stability, and in vitro ADME profiles, as well as the associated toxicity risks. We also summarize the research progress of these hybrid molecules in antitumor assays conducted using cellular and animal models and identify the current bottlenecks in their development, such as poor water solubility, incomplete druggability data, and the absence of standardized clinical translation paradigms. Finally, the paper explores the application prospects of emerging technologies, including AI-driven rational design, organoid models, and nano-delivery systems, in the R&D of quinolone hybrid molecules, offering a theoretical reference for the development of quinolone-based hybrid multi-target antitumor drugs. |
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