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Title

Use of natural molecules as anti-angiogenic inhibitors for vascular endothelial growth factor receptor

 

Authors

Subhojyoti Chatterjee1* & Biplab Bhattacharjee2

 

Affiliation

1Room No 4, Molecular Biophysics Unit (Annex Building); Indian Institute of Science, Bangalore -560012, India; 2PES Institute of technology, Bangalore

 

Email

subho.mbu.iisc@gmail.com; *Corresponding author

 

Article Type

Hypothesis

 

Date

Received November 25, 2012; Accepted November 26, 2012; Published December 19, 2012

 

Abstract

Angiogenesis refers to the formation of new blood vessels, controlled by certain chemicals, which on stimulation repairs damaged cells or form new ones. Other chemicals, called angiogenesis inhibitors, signal the process to stop, having only mild side effects and are non toxic to most healthy cells. In our study, attempt was made to find potent anti-angiogenic inhibitor (pazopanib was considered as a reference drug) for vascular endothelial growth factor receptor (VEGFR-1/FLT-1), which served as a molecular target, using natural agents targeting biological processes important in cancer. Hundreds of natural molecules were initially screened based on lipinskiís rule of five and the satisfying ones were taken for receptor-ligand interaction study using docking tools like HEX and quantum. Around fifteen molecules were taken as lead molecule and their binding pocket on VEGF was analyzed using SwissPDBviewer and Q-site finder. The investigational drug pazopanib was found to be interacting with leucine 32 and glutamine 30 in terms of hydrogen bond with the distance of 1.86 and 2.49 A0 respectively. Ames test for the molecules was predicted for probability of mutagenicity on molecular systems such as blood, cardiovascular system, gastrointestinal system; kidney, liver and lung were considered for further screening of the molecules. The natural molecules curcumin, epigallocatechin gallate (EGCG), barrigtozenol and finasteride were showing reliable interaction with VEGFR and their pharmacokinetics parameters were comparatively good than the pazopanib. The dietary product curcumin and EGCG can be cancer chemopreventive agents and the natural molecules barringtozenol and finasteride can be effective inhibitors for VEGFR. 

 

Keywords

Angiogenesis, VEGF, chemopreventive agent, pharmacokinetics study, Lipinskiís rule.

 

Citation

Chatterjee & Bhattacharjee,  Bioinformation 8(25): 1249-1254 (2012)
 

Edited by

P Kangueane

 

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.