Li Jianqin, Yang Yan, Wang Lei, Liu Quanli, Kang Xiaohong, Yang Yun
Oncology Department, The First Affiliated Hospital, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
Henan Province Engineering Research Center of Macromolecular Drug Technology Innovation, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
Int J Mol Med. 2025 Dec;56(6). doi: 10.3892/ijmm.2025.5646. Epub 2025 Sep 26.
The quinazolinone scaffold is widely present in natural compounds and serves as a core structural unit in various alkaloids. Its structural flexibility is a major advantage in anti‑tumor drug development. Characterized by a fused bicyclic system, this scaffold enables precise pharmacological modulation through targeted chemical modifications, allowing the regulation of multiple cell death pathways, including apoptosis, autophagy, ferroptosis, senescence, pyroptosis and necrosis. This review systematically describes the molecular mechanisms by which quinazolinone derivatives induce tumor cell death and critically evaluates their clinical translation potential. In addition, quinazolinone‑based agents approved by the Food and Drug Administration and those in preclinical development as targeted anti‑tumor therapies are summarized, providing new perspectives and methodological frameworks for advancing oncology drug discovery.
喹唑啉酮骨架广泛存在于天然化合物中,并作为各种生物碱的核心结构单元。其结构灵活性是抗肿瘤药物开发的一个主要优势。该骨架以稠合双环系统为特征,通过有针对性的化学修饰实现精确的药理调节,从而能够调控多种细胞死亡途径,包括凋亡、自噬、铁死亡、衰老、焦亡和坏死。本综述系统地描述了喹唑啉酮衍生物诱导肿瘤细胞死亡的分子机制,并对其临床转化潜力进行了批判性评估。此外,还总结了美国食品药品监督管理局批准的基于喹唑啉酮的药物以及处于临床前开发阶段的靶向抗肿瘤治疗药物,为推进肿瘤学药物发现提供了新的视角和方法框架。