Redefining the significance of quinoline containing compounds as potent VEGFR-2 inhibitors for cancer therapy

Abstract

Vascular endothelial growth factor receptor-2 (VEGFR-2), a tyrosine kinase receptor (TKR) is frequently overexpressed in most of the cancers. It plays a crucial part in tumor angiogenesis through mediating vital angiogenic cellular signals, including endothelial cell survival, proliferation, migration and vascular permeability. Due to the key importance in facilitated tumor vasculature, VEGFR-2 has emerged as a legit therapeutic target against cancer. Quinoline a fused heterocyclic scaffold with weak basicity can deliver a diverse degree of activity upon chemical substitution and attract considerable scientific attention. Quinoline containing compounds namely lenvatinib and cabozantinib have been approved as VEGFR-2 inhibitors for the management of various categories of cancer, while some drugs such as lucitanib and foretanib are currently under clinical evaluation. Some recently synthesized quinoline-(1H)-4 one derivative substituted at 3^rd, and 6^th position, and another compound substituted at 4^th position with 2-(3,4-dichlorophenyl)-1H-benzo[d]imidazol-6-amine have showed VEGFR-2 inhibition better than the standard drugs sorafenib and sunitinib, respectively (45 nM, and 40 nM, respectively). The quinoline analogs hold promise as VEGFR-2 inhibitors for future cancer treatment, with ongoing research addressing the structural refinement, potential toxicity and combination therapies. This review summarizes the role of VEGFR-2 in cancer progression, and quinoline containing compounds as VEGFR-2 inhibitors for cancer therapy.