Druggability and Binding Site Interaction Studies of Potential Metabolites Isolated from Marine Sponge Aurora globostellata against Human Epidermal Growth Factor Receptor-2.

M Sugappriya,Raj Bhaskaran,Arumugam Suresh,D Sudarsanam,Jerrine Joseph

doi:10.6026/97320630013261

Abstract

To study the involvement of compounds stigmasterol and oleic acid isolated from marine sponge Aurora globostellata and docking against the Human Epidermal Growth Factor Receptor-2 in breast cancer. The comparative molecular docking was performed with the natural compounds from marine sponge and the synthetic drugs used in breast cancer treatment against the target HER2. The molecular docking analysis was done using GLIDE in Schrodinger software package. The ADME properties were calculated using the Qikprop. The observation of the common binding site for all the ligands confirms the binding pocket; where the isolated compound Stigmasterol agrees well with the binding residues and thus can be optimized further to arrive at a molecule that has a high binding affinity and low binding constant. The results of the docking studies carried out on HER2 provide an insight for the compound stigmasterol to have drug like properties than oleic acid. These results are supportive to confirm the marine sponges as a better lead for cancer therapeutics.

Highlights

The present study focuses on the in-silico analysis of the naturally isolated compounds from marine sponges and compared with the results for the commercial drugs: Afinitor, Halaven, Ixabipilone, Lapatinib, Letrozole, Palbocilib, Raloxifene, and Tamoxifen
Docking Analysis: Molecular docking approach helps us in identifying best binding ligands with the protein target and helps in exploring new small molecular leads from natural sources with higher binding affinities
The Herceptin Fab domain was removed for the docking of commercial drugs with HER2

Summary

Introduction

The marine environment is complex with variations in pressure, salinity, temperature and biological habitats. The marine organisms have unique therapeutic properties. These have been explored and are yet to be proved [1]. The organisms living in oceans are unique with richest sources of new drug leads. Marine sponges are said to be the gold mines for the past 50 years, with respect to the diversity of secondary metabolites. Sponges produce wide array of compounds with varying carbon skeleton, by which the diseases can be suppressed at different points on focusing specific targets. The secondary metabolites produced are biologically active molecules not directly involved in normal functions of the organisms, which includes growth, reproduction or development [2,3]

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Conclusion