Abstract

PHARMACOPHORE MAPPING AND DOCKING STUDIES OF SOME BIOACTIVE COMPONENTS FOR ANTICANCER ACTIVITY TARGETING HER2

Rupanjali Bhattacharjya Sharma*, Mainu Borah and Surabhi Johari

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Abstract

The natural plant products are commonly occurring bioactive components used for drug discovery. The current approach reveals the use of natural plants derivatives in treating breast cancer targeting Human Epidermal growth Receptor (HER2). In order to obtain most potent inhibitors, different computer aided designing technologies like pharmacophore modelling, virtual screening and molecular docking studies were utilised. In order to identify the necessary chemical features of HER2 inhibitors, pharmacophore models were generated using Pharma Gist The screened molecules were filtered by applying Lipinski’s rule of five and molecular docking study using HER 6.3 package to refine the retrieved hits.The bioactive components were virtually screened in order to classify them as drug like molecules. The datasets of 7 components revealed that all of them although satisfy Lipsinki’s rule of five but not ADME/TOX rule. The detailed analysis predicted that the compound 3, Daucosterol satisfy L-rule as well as ADME/TOX prediction with low risk to HER2 inhibition. Also when the particular molecule was allowed to interact with HER2 protein, it showed binding energy of-257.34 kcal/mol which was quiet acceptable. Whereas other plant components also showed minimum binding energy but they were violation ADME/TOX rules so they were excluded from the current study. From the phytochemical and virtual screening, ligand-based pharmacophore modelling and docking studies, we concluded that our pharmacophore model, Model-3 can be used in order to identify new potent compounds from any chemical databases that may act as good leads against 4HRL. Docking of 7 bioactive anticancerous compounds was carried out and three compounds namely, comp1, comp 3 and comp7 exhibited minimum energy values and also followed all criteria of Lipinski’s properties but not ADME/TOX rule. And it was also observed that the compound 3, Daucosterol satisfy Lipinski’s-rule as well as ADME/TOX prediction with low risk to HER2 inhibition and therefore found to be highly potent inhibitors against 4HRL causing breast cancer. Hence, we concluded that the above mentioned compound can be used as inhibitors for treating breast cancer.

Keywords: Cancer, HER2, Pharmacophore, Docking, Inhibitor.