Design and Synthesis of Novel Vascular Disrupting Agents With Potential Chemotherapeutic Properties

Abstract

The term cancer is a widely universal label for a cluster of cells that can divide uncontrollably and invade the surrounding healthy tissue. Vascular targeting agents (VTAs) represent an important and emerging area of cancer therapy. VTAs are subdivided into two categories, anti-angiogenic agents and vascular disrupting agents (VDAs). Both biologics and small-molecule anticancer agents fall under the VDA umbrella. A significant number of the clinically-relevant, small-molecule VDAs function through a binding event to the colchicine site on the α/β-tubulin hetero-dimer, inhibiting microtubule formation. Interestingly, these VDAs have a pronounced effect on the morphology of the endothelial cells lining tumor vasculature ultimately damaging these microvessels thus starving tumors of necessary oxygen and nutrients. This study explains the synthesis of a few novel potential VDAs that have been designed.