Executive Summary : | Despite tremendous development in cancer detection and treatment, mortality is still high and no permanent cures are available. As Cancer is a multifactorial disease and there is cross-talk between various pathways to control a particular function So one drug one target is not a useful strategy as compared to the multi-targeted approach. By utilizing a multitargeted approach microtubule de-polymerization and MetAP2 enzyme inhibition together are some of the promising targets for the development of anti-cancer agents. Individual targeting of each, microtubules, and MetAP-2 are not much effective for the complete cure of cancer. Microtubule targeting agents disrupt the dynamic equilibrium of tubulin-microtubule and block cell division at the G-2/M phase that leads to the induction of the mitochondrial apoptosis and due to its vascular disrupting property, they destroy the existing blood vessels, and inhibition of MetAP-2 enzyme results in inhibition of new blood vessel formation. So, targeting these two proteins simultaneously results in the development of a new effective target that may eradicate cancer. Thus in the current research proposal, it has been proposed to design, synthesize, and biological evaluation of Combretastatin-based novel multitargeting ligands that can act as tubulin polymerization inhibitors, vascular disrupting, and antiangiogenic agents. |