Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500037, India.
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500037, India.
Eur J Med Chem. 2021 Apr 15;216:113334. doi: 10.1016/j.ejmech.2021.113334. Epub 2021 Mar 3.
Small-molecule kinase inhibitors are being continuously explored as new anticancer therapeutics. Kinases are the phosphorylating enzymes which regulate numerous cellular functions such as proliferation, differentiation, migration, metabolism, and angiogenesis by activating several signalling pathways. Kinases have also been frequently found to be deregulated and overexpressed in cancerous tissues. Therefore, modulating the kinase activity by employing small molecules has emerged as a strategic approach for cancer treatment. On the other hand, oxindole motifs have surfaced as privileged scaffolds with significant multi-kinase inhibitory activity. The present review summarises recent advances in the development of oxindole based kinase inhibitors. The role of distinguished structural frameworks of oxindoles, such as 3-alkenyl oxindoles, spirooxindoles, 3-iminooxindoles and similar hydrazone derivatives have been described based on their kinase inhibition potential. Furthermore, the design strategies, mechanism of actions, structure activity relationships (SARs) and their mode of interaction with target protein have been critically highlighted.
小分子激酶抑制剂作为新型抗癌治疗药物正在不断被探索。激酶是磷酸化酶,通过激活多种信号通路来调节许多细胞功能,如增殖、分化、迁移、代谢和血管生成。激酶也经常在癌组织中发现失调和过度表达。因此,通过使用小分子来调节激酶活性已成为癌症治疗的一种策略。另一方面,吲哚酮基序已成为具有显著多激酶抑制活性的优势支架。本综述总结了基于吲哚酮的激酶抑制剂的最新进展。根据其激酶抑制潜力,描述了吲哚酮的不同结构框架(如 3-烯基吲哚酮、螺吲哚酮、3-亚氨基吲哚酮和类似的腙衍生物)的作用。此外,还重点强调了设计策略、作用机制、构效关系(SAR)及其与靶蛋白的相互作用方式。