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Drug Res (Stuttg) 2014; 64(01): 23-30
DOI: 10.1055/s-0033-1351314
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Synthesis, Structure Activity Relationships and Biological Activity Evaluation of Novel Spirocyclic Thiazolidin-4-ones as Potential Anti-Breast Cancer and Epidermal Growth Factor Receptor Inhibitors

D. H. Fleita
1   Department of Chemistry, American University in Cairo, New Cairo, Egypt
,
O. K. Sakka
1   Department of Chemistry, American University in Cairo, New Cairo, Egypt
,
R. M. Mohareb
2   Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt
› Author Affiliations
Further Information

Publication History

received 30 March 2013

accepted 09 July 2013

Publication Date:
15 August 2013 (online)

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Abstract

A series of triazaspiro[4.5]dec-8-ene benzylidine derivatives containing thiazolidinone ring system (6–18) have been designed, synthesized and their biological activities evaluated as potential epidermal growth factor receptor inhibitors. Among them, 9-amino-2-(4-nitrobenzylidene)-3-oxo-4-phenyl-7-thioxo-1-thia-4,6,8-triazaspiro[4.5]dec-8-ene-10-carbonitrile (18) displayed the most potent inhibitory activity (IC50=6.355 µM). Antiproliferative assay results indicated that compound 18 exhibited moderate antiproliferative activity against MCF-7 cell line in vitro; with GI50 value of 30.6 µM. In addition, compounds 7 and 15 displayed the highest antiproliferative activity at a common GI50 value of 10.8 µM. Docking simulation was performed to determine the probable binding model and to pursuit information regarding the activity of compound 18. Based on the preliminary results, compound 18 could be used as an attractive building block for designing potential epidermal growth factor receptor inhibitors.

Key words

spiro-thiazolidin-4-one - EGFR - antiproliferative - structure activity relationship
 

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