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Arzneimittelforschung 2012; 62(12): 554-560
DOI: 10.1055/s-0032-1323759
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Virtual Screening and Synthesis of New Chemical Scaffolds as VEGFR-2 Kinase Inhibitors

M. S. Elsayed
1   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ainshams University, Abbasia, Cairo, Egypt
,
M. E. El-Araby
2   Department of Organic Chemistry, Faculty of Pharmacy Helwan University, Helwan, Egypt
,
R. T. Serya
1   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ainshams University, Abbasia, Cairo, Egypt
,
K.A. M. Abouzid
1   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ainshams University, Abbasia, Cairo, Egypt
› Author Affiliations
Further Information

Publication History

received 01 June 2012

accepted 13 August 2012

Publication Date:
21 September 2012 (online)

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Abstract

Background:

VEGFR-2 tyrosine kinase inhibitors are currently receiving high interest in drug discovery process as anticancer agents. We have used virtual screening techniques in order to discover new scaffolds that can be used for developing new VEGFR-2 kinase inhibitors.

Method:

Similarity ensemble approach was used to reduce the chemical space of ZINC database to select a subset of compounds. A validated structure-based pharmacophore was developed and adopted to screen the selected subset. Initial hits mapped to the pharmacophore were filtered using docking and scoring. Selected compounds were synthesized and biologically tested.

Results:

Compound 9 showed very good cytotoxicity profile against the NCI 60 cancer cell lines, while compound 8 showed reasonable inhibition of VEGFR-2 tyrosine kinase.

Conclusion:

Stepwise virtual screening of databases such as ZINC may result in new scaffolds for developing VEGFR-2 kinase inhibitors.

Key words

SEA prediction - pharmacophore - docking - VEGFR-2
 

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