Title:Structure Based Drug Design and Molecular Docking Studies of Anticancer Molecules Paclitaxel, Etoposide and Topotecan using Novel Ligands
Volume: 17
Issue: 2
Author(s): Manisha Yadav, Swasti Dhagat and Jujjavarapu S. Eswari*
Affiliation:
- Department of Biotechnology, National Institute of Technology, Raipur,India
Keywords:
Structure based drug design, molecular docking, docking score, novel ligands, anti-cancer molecules, cancer.
Abstract:
Background: Tubulin is the biochemical target for several clinically used anticancer
drugs as it helps in the formation of mitotic spindle during mitosis stage of cell division. Many of
the anti-cancer drugs are known to interact with tubulin and microtubules including some plant alkaloids,
such as paclitaxel, etoposide and topotecan. In silico drug design of these molecules were
performed prior to testing these drugs in vitro. In silico drug design of these anti-cancer drugs becomes
a challenge due to the complex structure of target protein. This challenge was overcome by
predicting the structure of the target protein (tubulin) by homology modeling.
Methods: In this study, computer aided drug designing approach was applied to predict the suitable
docking site in target protein and the interaction of tubulin protein with paclitaxel, etoposide
and topotecan was explored by molecular docking using Schrödinger software. Docking score and
glide energy were determined with ligands to validate their anticancer properties.
Results: The results indicate that etoposide is the best drug for tubulin with a docking score of -
4.916 and glide energy of -46.470 kcal/mol compared to paclitaxel and topotecan.
Conclusion: The testing of these drugs in silico provides an alternate to in vitro testing of these
molecules on cancer cell lines which is a time and cost intensive process. The in silico study of parameters,
such as docking score and glide energy, will help pharmacists in developing new molecules
as targets for cancers in a time and cost-effective manner.
