Department of Pharmaceutical Chemistry, ISF College of Pharmacy, GT Road, Ghal Kalan, Moga, 142001, Punjab, India.
Department of Pharmaceutical Chemistry, ISF College of Pharmacy, GT Road, Ghal Kalan, Moga, 142001, Punjab, India.
Eur J Med Chem. 2021 Oct 5;221:113495. doi: 10.1016/j.ejmech.2021.113495. Epub 2021 May 5.
Aurora kinases are a family of serine/threonine kinases that play a crucial role in cell proliferation through the regulation of mitotic spindles. These kinases are the regulatory proteins localized in the various phases of the cell cycle and are involved in centrosome maturation, chromosome alignment, chromosomal segregation, and cytokinesis. They have emerged as one of the validated drug targets for anticancer drug discovery as their overexpression has been implicated in the pathogenesis of various carcinomas. Inhibitors of Aurora kinases induce growth inhibition and apoptosis in a variety of tumor cells. Hence, the design and development of Aurora kinase inhibitors have been widely explored in recent years by the scientific community as potential anticancer agents. Various Aurora kinase inhibitors have been under preclinical and clinical investigations as antitumor agents. This review summarizes the recent strategies of various researchers for the design and development of Aurora kinase inhibitors belonging to different structural classes. Their bioactivity, SARs, molecular modelling, and mechanistic studies have also been described. The comprehensive compilation of research work carried out in the field will provide inevitable scope for the design and development of novel drug candidates with better selectivity and efficacy. The review is constructed after the exhaustive research in this discipline and includes the papers from 2011 to 2020.
极光激酶是丝氨酸/苏氨酸激酶家族，通过调节有丝分裂纺锤体在细胞增殖中发挥关键作用。这些激酶是定位于细胞周期各个阶段的调节蛋白，参与中心体成熟、染色体排列、染色体分离和胞质分裂。它们已成为抗癌药物发现的验证药物靶点之一，因为它们的过度表达与各种癌的发病机制有关。极光激酶抑制剂在各种肿瘤细胞中诱导生长抑制和细胞凋亡。因此，近年来科学界广泛探索了极光激酶抑制剂的设计和开发，将其作为潜在的抗癌药物。各种极光激酶抑制剂作为抗肿瘤药物正在进行临床前和临床研究。本综述总结了最近不同研究人员设计和开发属于不同结构类别极光激酶抑制剂的策略。还描述了它们的生物活性、SAR、分子建模和机制研究。对该领域开展的研究工作的全面汇编将为设计和开发具有更好选择性和疗效的新型候选药物提供必要的范围。该综述是在对该学科进行详尽研究的基础上构建的，包括 2011 年至 2020 年的论文。
