Sulfonamide Derivatives as Potent VEGFR-2 Inhibitors: Advances and Therapeutic Perspectives: A Comprehensive Review

The master of angiogenesis, vascular endothelial growth factor receptor 2 (VEGFR-2), is a prime target for anticancer drug development. Sulfonamide derivatives have been shown to be extremely versatile scaffolds as they possess favorable physicochemical properties and are pharmacologically easily accessible among the variety of backbones employed for VEGFR-2 inhibition. Here we review on VEGFR2-targetable sulfonamide derivatives with respect to their structural requirement, binding mode and pharmacological significance. In the last section computational methods like QSAR modeling, graph-based docking and future quantum computation have been presented which contribute toward speeding up rational drug design. On one hand, hydrogen bond strengthening and π-π stacking in combination with electronic delocalization have been reported to tune the protein-ligand interaction profile 96, whereas on the other hand nanotechnology enabled delivery system (e.g., mesoporous silica NPs with bio-molecular capping) provide a promising platform to promote solubility, selection and site-specific release. The way to high selectivity, resistance bypassing and environmental bioavailability is still long but nanotechnology and quantum simulation provided with an interdisciplinary designing approach show great capacity for innovation. Collectively, sulfonamide derivatives are an interesting class of a next-generation antiangiogenic drugs with a high potential for cancer therapy and personalized medicine.