Department of Pharmaceutical Sciences, Dr. Harisingh Gour University, Sagar 470003, MP, India.
Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, P. O. Box 17020, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India.
Bioorg Med Chem. 2022 Jan 1;53:116534. doi: 10.1016/j.bmc.2021.116534. Epub 2021 Nov 27.
Kinases are considered as important signalling enzymes that illustrate 20% of the druggable genome. Human kinase family comprises >500 protein kinases and about 20 lipid kinases. Protein kinases are responsible for the mechanism of protein phosphorylation. These are necessary for regulation of various cellular activities including proliferation, cell cycle, apoptosis, motility, growth, differentiation, etc. Their deregulation leads to disruption of many cellular processes leading to different diseases most importantly cancer. Thus, kinases are considered as valuable targets in different types of cancer as well as other diseases. Researchers around the world are actively engaged in developing inhibitors based on distinct chemical scaffolds. Indole represents as a versatile scaffold in the naturally occurring and bioactive molecules. It is also used as a privileged scaffold for the target-based drug design against different diseases. This present article aim to review the applications of indole scaffold in the design of inhibitors against different tyrosine kinases such as epidermal growth factor receptors (EGFRs), vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptors (PDGFRs), etc. Important structure activity relationships (SARs) of indole derivatives were discussed. The present work is an attempt to summarize all the crucial structural information which is essential for the development of indole based tyrosine kinase inhibitors with improved potency.
激酶被认为是重要的信号酶，占可用药基因组的 20%。人类激酶家族包括>500 种蛋白激酶和约 20 种脂质激酶。蛋白激酶负责蛋白质磷酸化的机制。这些酶对于调节各种细胞活动是必要的，包括增殖、细胞周期、细胞凋亡、运动、生长、分化等。它们的失调导致许多细胞过程的破坏，导致不同的疾病，最重要的是癌症。因此，激酶被认为是不同类型癌症以及其他疾病的有价值的靶点。世界各地的研究人员都在积极开发基于不同化学结构的抑制剂。吲哚作为一种在天然存在和生物活性分子中具有多功能的结构，也被用作针对不同疾病的基于靶标的药物设计的优势结构。本文旨在综述吲哚骨架在设计针对不同酪氨酸激酶（如表皮生长因子受体（EGFRs）、血管内皮生长因子受体（VEGFRs）、血小板衍生生长因子受体（PDGFRs）等）抑制剂中的应用。讨论了吲哚衍生物的重要构效关系（SARs）。本工作旨在总结所有关键的结构信息，这些信息对于开发基于吲哚的具有改善效力的酪氨酸激酶抑制剂是必不可少的。
