Umesh Yadava, Hariom Gupta, M Roychoudhury
Department of Physics, DDU Gorakhpur University, Gorakhpur (U.P.), India.

ABSTRACT

The Himalayan yew (Taxus Wallichiana) is a tree or a large shrub growing on either sides of Himalayas from Afganistan to Burma1. The long and legendry history of the yew as a poison and the more recent discovery of the antitumer activity of some of its constituents have made the genus Taxus. The taxane diterpenoids (taxoids) 10, 13-deacetyl-abeo-baccatin-IV (I) and 5-acetyl-2-deacetoxydecinnamoyl-taxinine-0.29hydrate (II) were isolated from the needles and heartwood respectively of the Taxus Wallichiana (Himalayan yew) which were expected to possess interesting pharmacological properties. Over the past decade, considerable attention has been paid to taxoids (Taxane diterpenoids), whose archetype is paclitaxel (TaxolTM), a promising cancer chemotherapeutic agent2. In fact taxol was found to induce assembly of tubulin in to microtubules, and more importantly, that the drug actually stabilizes them to the extent that mitosis is disrupted3. Such a novel mode of action was believed to make taxol a prototype for a new class of anticancer drugs. Although a numerous X-ray investigations have been performed on this and the related molecules, there is much heated debate about the active conformations of this anticancer drug4. These prompted us to undertake the X-ray crystallographic study5,6 and the present theoretical studies on taxoids (I) and (II). In the present work, Molecular Modeling and Docking studies have been carried out for the above compounds along with the original compound Taxol with Microtubule (PDB ID:1TUB) as target using Autodock and Schrodinger suite of programs to understand the mode of binding and the results have been discussed. .Read more…