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In silico screening of epidermal growth factor receptor (EGFR) in the tyrosine kinase domain through a medicinal plant compound database

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Abstract

The unregulated epidermal growth factor receptor tyrosine kinase (ErbB1-TK or EGFR-TK) protein is involved in the proliferation of more than 50% of all cancer types. The reduction of EGFR-TK activity by small or medium-sized molecules has been proven to be an effective treatment for cancer. There is a widespread belief that Chinese medicinal herbs are active against several diseases, including various types of cancer. In this study, 29,960 compounds from the Chemiebase medicinal compound database were virtually screened against the EGFR-TK using AutoDock4.0, GOLD and GLIDE (XP). The results revealed eight potential hits: CAS nos. 104096-45-9, 112649-21-5, 113866-89-0, 142608-98-8, 142608-99-9, 144761-33-1, 155233-17-3 and 80510-05-0. These compounds have been reported to show anticancer activities in the literature. With the help of SiMMap and MOE interaction analysis, the protein–ligand interaction patterns between the functional groups of these compounds and the binding pocket residues were analyzed. Hydrogen bonding and hydrophobic forces are the main components of the interactions of these hits, similar to those observed for the known inhibitors erlotinib, gefitinib and AEE. The physicochemical filter indicates that compounds CAS nos. 104096-45-9 and 144761-33-1 are likely to be potential leads in the drug discovery process.

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Acknowledgments

This work was supported by the Thailand Research Fund [TRF project code MRG4980061, TRF Senior Research Scholars (RTA 5380010)], BRC 13/2551, Faculty of Science, Graduate School Research Fund, Kasetsart University, and Kasetsart University Research and Development Institute. We would like to thank the Interdisciplinary Graduate Program in Genetic Engineering, Kasetsart University, for providing SYBYL 7.3, as well as the Institute for Theoretical Chemistry, University of Vienna, Austria, for generously providing the MOE and Schrödinger programs as well as computing time and research facilities. The usage of the GOLD program was allowed by the National Center of Excellence in Petroleum, Petrochemical Technology and Advanced Materials. Thanks are due to Dr. Anton Bayer and Dr. Witcha Treesuwan for their suggestions.

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Authors and Affiliations

  1. Department of Biochemistry, Kasetsart University, Bangkok, Thailand, 10900

    Orathai Sawatdichaikul & Kiattawee Choowongkomon

  2. Department of Chemistry, Kasetsart University, Bangkok, Thailand, 10900

    Supa Hannongbua & Chak Sangma

  3. Institute for Theoretical Chemistry, University of Vienna, Vienna, Austria, 1090

    Peter Wolschann

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  1. Orathai Sawatdichaikul
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  2. Supa Hannongbua
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Correspondence to Kiattawee Choowongkomon.

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Sawatdichaikul, O., Hannongbua, S., Sangma, C. et al. In silico screening of epidermal growth factor receptor (EGFR) in the tyrosine kinase domain through a medicinal plant compound database. J Mol Model 18, 1241–1254 (2012). https://doi.org/10.1007/s00894-011-1135-z

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