DOCKING ANALYSIS OF SUBSTITUTED 2-PHENYL-1H-INDOL-3YL GLYOXYLAMIDE AS INHIBITORS OF TUBULIN POLYMERIZATION- POTENTIAL NEW ANTICANCER AGENTS

Indibulin (N-(pyridin-4-yl)-[1-(4-chlorbenzyl)-indol-3-yl]-glyoxyl-amid; ZIO-301 or D-24851) is a novel synthetic, orally active anti-mitotic agent that binds tubulin, destabilizes microtubulin polymerization, and arrests tumor cell growth at the G2/M phase. Its tubulin binding site is distinct from that of other microtubulin inhibitors such as taxanes, colchicines, and vinca alkaloids. Many researchers were motivated by this achievement of vinblastine and vincristine (vinca alkaloids) and developed the indole-based new anticancer chemical entities. Indole containing anticancer molecules has shown their anticancer properties through the diverse mechanism of action. The majority of the synthetic indoles have a structural analogy to natural anticancer products (vinca alkaloids or combretastatin) and exhibited anticancer activity through tubulin interactions. The indole ring system is an essential part of many tubulin inhibitors identified in recent years. The Substituted 2-Phenyl-1H-Indol-3yl Glyoxylamidewere was computationally designed and energy minimized. All the designed compounds show zero violations of the rule of 5, which indicates drug-likeness properties and good bioavailability. Among these, several aryl/ heteroaryl substituted indolylglyoxyamides have shown good inhibition towards tubulin polymerization.