Title

Authors

Palani Kirubakaran¹, Roopa Kothapalli², Kh. Dhanachandra Singh¹, Selvaraman Nagamani¹, Subramanian Arjunan³, Karthikeyan Muthusamy¹*
 

Affiliation

¹Department of Bioinformatics, Alagappa University, Karaikudi, Tamil Nadu, India; ²Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; ³Human embryonic stem cell Laboratory, Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

Email

mkbioinformatics@gmail.com; *Corresponding author

Phone

+91 4565-230725

Fax

+914565 225202

Article Type

Hypothesis

Date

Received December 28, 2010; Accepted February 21, 2011; Published April 22, 2011

Abstract

Glioblastoma multiforme (GBM) is considered to be the most common and often deadly disorder which affects the brain. It is caused by the over expression of proteins such as ephrin type-A receptor 2 (EphA2), epidermal growth factor receptor (EGFR) and EGFRvIII. These 3 proteins are considered to be the potential therapeutic targets for GBM. Among these, EphA2 is reported to be over-expressed in ~90% of GBM. Herein we selected 35 compounds from marine actinomycetes, 5 in vitro and in vivo studied drug candidates and 4 commercially available drugs for GBM which were identified from literature and analysed by using comparative docking studies. Based on the glide scores and other in silico parameters available in Schrödinger, two selected marine actinomycetes compounds which include Tetracenomycin D and Chartreusin exhibited better binding energy among all the compounds studied in comparative docking. In this study we have demonstrated the inhibition of the 3 selected targets by the two bioactive compounds from marine actinomycetes through in-silico docking studies. Furthermore molecular dynamics simulation were also been performed to check the stability and the amino acids interacted with the 3 molecular targets (EphA2 receptor, EGFR, EGFRvIII) for GBM. Our results suggest that Tetracinomycin D and Chartreusin are the novel and potential inhibitor for the treatment of GBM.

Keywords

Glioblastoma multiforme, EphA2, EGFR, EGFRvIII, docking and molecular dynamics.

Citation

Kirubakaran et al. Bioinformation 6(3): 100-106 (2011)

Edited by

A Cherkosav

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.