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Bioinformation. 2015 Jul 31;11(7):322-9. doi: 10.6026/97320630011322. eCollection 2015.

Molecular docking based screening of novel designed chalcone series of compounds for their anti-cancer activity targeting EGFR kinase domain.

Author information

1
Research Scholar, Department of Pharmaceutical Sciences, JNTUK, Kakinada-533003, Andhra Pradesh, India.
2
Department of Pharmaceutical Chemistry, University College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, Andhra Pradesh-530003, Andhra Pradesh, India.
3
Department of Pharmaceutical Chemistry, Nirmala College of Pharmacy, Mangalagiri, Atmakur Rural, Andhra Pradesh 522503, Andhra Pradesh, India.
4
Innovative Informatica Technologies, Hyderabad - 500 049, Andhra Pradesh, India.

Abstract

Epidermal growth factor receptors (EGFR) are critical for the growth of many tumors and expressed at high levels in about one third of epithelial cancers. Hence, blockade of the binding sites for EGFR has been hypothesized as an effective anti-cancer therapy. Chalcone derivative compounds have been shown to be highly effective anti-cancer agents, however there are still so many novel derivatives possible, one of which might get us the best targeted EGFR inhibitor. In this effort directed towards the discovery of novel, potent anti-tumor agents for the treatment of cancer, in the present study a library of novel chalcone series of compounds has been designed and evaluated for their anti-cancer activity targeting EGFR kinase domain using various computational approaches. Among the twenty five novel designed chalcone series of compounds, all of them have found to be successfully docking inside the active binding domain of EGFR receptor target with a binding energy in a range of -6.10 to -9.25 Kcal/mol with predicted IC50 value range of 33.50 micor molar to 164.66 nano molar respectively. On the other hand, calculated 2DQSAR molecular descriptor properties of the compounds showed promising ADME parameters and found to be well in compliance with Lipinski׳s rule of five. Among all the twenty five compounds tested, compound 21 ((2E)-3-(anthracen-9-yl)-1-phenylprop-2-2n-1- one) was found to be the best lead like molecule with a binding energy of -9.25 kcal/mol with predicted IC50 value of 164.66 nano molar. Conclusively, novel designed compound 21 of the present study have shown promising anti-cancer potential worth considering for further evaluations.

KEYWORDS:

ADME; EGFR kinase domain; QSAR; anti-cancer; chalcones; docking

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