取代喹唑啉类化合物在癌症治疗中与多个靶点相互作用的潜力。
Potential of substituted quinazolines to interact with multiple targets in the treatment of cancer.
机构信息
Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, 600 Forbes Avenue, Pittsburgh, PA 15282, United States.
College of Pharmacy, University of Oklahoma Health Science Center, 1110 North Stonewall, Oklahoma City, OK 73117, United States.
出版信息
Bioorg Med Chem. 2021 Apr 1;35:116061. doi: 10.1016/j.bmc.2021.116061. Epub 2021 Feb 12.
The efficacy of quinazoline-based antiglioma agents has been attributed to their effects on microtubule dynamics. The design, synthesis and biological evaluation of quinazolines as potent inhibitors of multiple intracellular targets, including microtubules and multiple RTKs, is described. In addition to the known ability of quinazolines 1 and 2 to cause microtubule depolymerization, they were found to be low nanomolar inhibitors of EGFR, VEGFR-2 and PDGFR-β. Low nanomolar inhibition of EGFR was observed for 1-3 and 9-10. Compounds 1 and 4 inhibited VEGFR-2 kinase with activity better than or equal to that of sunitinib. In addition, compounds 1 and 2 had similar potency to sunitinib in the CAM angiogenesis assay. Multitarget activities of compounds in the present study demonstrates that the quinazolines can affect multiple pathways and could lead to these agents having antitumor potential caused by their activity against multiple targets.
基于喹唑啉的抗肿瘤药物的疗效归因于它们对微管动力学的影响。本文描述了作为多种细胞内靶点（包括微管和多种 RTKs）的有效抑制剂的喹唑啉的设计、合成和生物评价。除了已知的喹唑啉 1 和 2 能够引起微管解聚的能力外，它们还被发现是 EGFR、VEGFR-2 和 PDGFR-β 的低纳摩尔抑制剂。1-3 和 9-10 对 EGFR 具有低纳摩尔抑制作用。化合物 1 和 4 对 VEGFR-2 激酶的抑制活性优于或等于舒尼替尼。此外，化合物 1 和 2 在 CAM 血管生成测定中与舒尼替尼具有相似的效力。本研究中化合物的多靶点活性表明，喹唑啉类化合物可以影响多种途径，并可能导致这些药物具有抗肿瘤潜力，因为它们对多种靶点的活性。
Zotero 插件