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; O. K. Sakka; R. M. Mohareb

doi:10.1055/s-0033-1351314

Drug Research, Inhaltsverzeichnis

Drug Res (Stuttg) 2014; 64(01): 23-30
DOI: 10.1055/s-0033-1351314

Original Article

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

¹Department of Chemistry, American University in Cairo, New Cairo, Egypt

,

O. K. Sakka

¹Department of Chemistry, American University in Cairo, New Cairo, Egypt

,

R. M. Mohareb

²Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt

› Institutsangaben

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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Referenzen

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