To Design Novel Derivatives of Noscapine (We Called as Fourth Generation) Using Structure Based Computer Aided Molecular Designing Techniques

Abstract

Microtubules are major cytoskeletal structures responsible for maintaining genetic stability during cell division. The dynamics of these polymers is absolutely crucial for this function. Interference with microtubules dynamics often leads to programmed cell death and thus microtubule-binding drugs such as paclitaxel, docetaxel and the vinca alkaloids are currently used to treat various malignancies in the clinic. However, these chemotherapy drugs are confounded by complications with toxicity, owing to their non-selective action and extreme overpolymerizing effects (taxanes) or depolymerizing effects (vincas) on microtubules. Besides toxicity, hydrophobic nature of these drugs confers insolubility necessitating the use of vehicles (such as Tween-80) that many a time cause extreme hypersensitivity reactions. Therefore, there is an urgent need to explore novel tubulin-binding agents that are significantly effective and comparatively less toxic compared to currently available drugs.