Therapeutic Insights of Indole Scaffold-Based Compounds as Protein Kinase Inhibitors

Abstract

Cancer is deemed to be one of the most severe diseases, which is accountable for the elevated mortality rate after cardiovascular diseases. Despite the huge numbers of drugs that were approved by the USFDA to combat the prevalence of cancer, the resistance of the diverse cancer types to the current medications as well as their high toxicity becomes an obstacle in cancer therapy. Thus, the developing of new medications with improved selectivity and efficiency to cure various types of cancer disease is still an imperative goal. Kinases are phosphorylating enzymes that catalyze the transfer of phosphate from ATP to tyrosine, serine and threonine residues of proteins, which leads to the activation of varied signaling pathways that regulate various cellular functions such as differentiation, proliferation, migration and angiogenesis. Abnormal phosphorylation leads to various diseases such as cancer, overexpression of kinases was frequently observed in different cancerous tissues. Thus, the suppression of the kinase activity has stood out as a strategic pathway for cancer therapy. Otherwise, indole core has displayed as a privileged scaffold with promising anticancer properties and multi-kinase suppression effect. This review presents various indole-based anticancer agents as kinase inhibitors in the recent decade. In addition, the various interactions of indole derivatives within the active pocket of different kinases have been highlighted. This review article comprises research reports from 2014 until the present.