Document Type
Article
Rights
This item is available under a Creative Commons License for non-commercial use only
Disciplines
1. NATURAL SCIENCES, 1.4 CHEMICAL SCIENCES, Organic Chemistry, Biochemistry and molecular biology, Medicinal chemistry
Abstract
The structure-activity relationships of antiproliferative β-lactams, focusing on modifications at the 4-position of the β-lactam ring, is described. Synthesis of this series of compounds was achieved utilizing the Staudinger and Reformatsky reactions. The antiproliferative activity was assessed in MCF-7 cells, where the 4-(4-ethoxy)phenyl substituted compound 26 displayed the most potent activity with an IC50 value of 0.22 μM. The mechanism of action was demonstrated to be by inhibition of tubulin. Cell exposure to combretastatin A-4 and 26 led to arrest of MCF-7 cells in the G2/M phase of the cell cycle and induction of apoptosis. Additionally, mitotic catastrophe for combretastatin A-4 and for 26 was demonstrated in breast cancer cells for the first time, as evidenced by the formation of giant, multinucleated cells.
DOI
https://doi.org/10.1016/j.ejmech.2011.07.039
Recommended Citation
O'Boyle, N. et al (2013). Synthesis, biochemical and molecular modelling Studies of antiproliferative azetidinones causing microtubule disruption and mitotic catastrophe. European Journal of Medicinal Chemistry, 2011, 46, pp. 4595 – 4607. doi: http://dx.doi.org/10.1016/j.ejmech.2011.07.039
Included in
Biochemistry Commons, Chemical Actions and Uses Commons, Enzymes and Coenzymes Commons, Heterocyclic Compounds Commons, Medicinal Chemistry and Pharmaceutics Commons, Organic Chemicals Commons
Publication Details
European Journal of Medicinal Chemistry, 2011, Vol. 46, Pages 4595 – 4607
DOI: http://dx.doi.org/10.1016/j.ejmech.2011.07.039