Institute of Pharmacy & Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, China.
Institute of Chemistry and Materials Science, Hengyang Normal University, Hengyang 421001, China.
Bioorg Med Chem. 2019 Feb 1;27(3):568-577. doi: 10.1016/j.bmc.2018.12.032. Epub 2018 Dec 24.
Quinazoline was originally utilized as an anti-tumor treatment, and its various derivatives can be directly extracted from plants. In recent years, protein kinases (PK) have been well recognized in the development of tumor drugs. Functionally, PK serves a vital role in the apoptosis, proliferation, differentiation, migration and cell cycle of tumor cells. Due to its good physicochemical properties, quinazoline skeleton, a superior type of PK inhibitor, has been extensively used in anti-tumor drug design. An increasing number of studies on quinazoline synthesis have been reported and used by different groups to effectively develop novel derivatives. Thus, several studies have been approved for the use of quinazoline derivatives as inhibitors of other kinases, including Src and histone deacetylase. The aim of the present review was to summarize the mechanism of quinazoline compounds as PK inhibitors, their biological structure-activity relationship such as the substituted quinazoline compounds with different functional groups in the apoptotic process, and their effect on the proliferation of tumor cells. The development of novel agents based on the antitumor functions of quinazoline molecular compounds may improve the clinical outcomes of the affected population, particularly in patients with cancer.
喹唑啉最初被用作抗肿瘤治疗药物，其各种衍生物可直接从植物中提取。近年来，蛋白激酶（PK）在肿瘤药物的开发中得到了广泛的认可。在功能上，PK 在肿瘤细胞的凋亡、增殖、分化、迁移和细胞周期中起着至关重要的作用。由于其良好的物理化学性质，喹唑啉骨架作为一种优秀的 PK 抑制剂类型，已广泛应用于抗肿瘤药物设计中。越来越多的关于喹唑啉合成的研究被不同的研究小组报道并应用，以有效地开发新型衍生物。因此，已有几项研究批准将喹唑啉衍生物用作其他激酶（包括Src 和组蛋白去乙酰化酶）的抑制剂。本综述的目的是总结喹唑啉类化合物作为 PK 抑制剂的作用机制，以及其在凋亡过程中具有不同功能基团的取代喹唑啉化合物等生物结构-活性关系，及其对肿瘤细胞增殖的影响。基于喹唑啉分子化合物的抗肿瘤功能开发新型药物可能会改善受影响人群的临床结局，尤其是癌症患者的临床结局。
