387850-75-1Relevant academic research and scientific papers
3-Vinylazetidin-2-Ones: Synthesis, antiproliferative and tubulin destabilizing activity in MCF-7 and MDA-MB-231 Breast Cancer Cells
Wang, Shu,Malebari, Azizah M.,Greene, Thomas F.,O’Boyle, Niamh M.,Fayne, Darren,Nathwani, Seema M.,Twamley, Brendan,McCabe, Thomas,Keely, Niall O.,Zisterer, Daniela M.,Meegan, Mary J.
, (2019)
Microtubule-targeted drugs are essential chemotherapeutic agents for various types of cancer. A series of 3-vinyl-β-lactams (2-azetidinones) were designed, synthesized and evaluated as potential tubulin polymerization inhibitors, and for their antiproliferative effects in breast cancer cells. These compounds showed potent activity in MCF-7 breast cancer cells with an IC50 value of 8 nM for compound 7s 4-[3-Hydroxy-4-methoxyphenyl]-1-(3,4,5-trimethoxyphenyl)-3-vinylazetidin-2-one) which was comparable to the activity of Combretastatin A-4. Compound 7s had minimal cytotoxicity against both non-tumorigenic HEK-293T cells and murine mammary epithelial cells. The compounds inhibited the polymerisation of tubulin in vitro with an 8.7-fold reduction in tubulin polymerization at 10 μM for compound 7s and were shown to interact at the colchicine-binding site on tubulin, resulting in significant G2/M phase cell cycle arrest. Immunofluorescence staining of MCF-7 cells confirmed that β-lactam 7s is targeting tubulin and resulted in mitotic catastrophe. A docking simulation indicated potential binding conformations for the 3-vinyl-β-lactam 7s in the colchicine domain of tubulin. These compounds are promising candidates for development as antiproiferative microtubule-disrupting agents.
Synthesis and antiproliferative evaluation of 3‐chloroazetidin‐2‐ones with antimitotic activity: Heterocyclic bridged analogues of combretastatin a‐4
Fayne, Darren,Greene, Thomas F.,Khan, Mohemmed Faraz,Malebari, Azizah M.,McCabe, Thomas,Meegan, Mary J.,Nathwani, Seema M.,O’boyle, Niamh M.,Twamley, Brendan,Wang, Shu,Zisterer, Daniela M.
, (2021/11/13)
Antimitotic drugs that target tubulin are among the most widely used chemotherapeutic agents; however, the development of multidrug resistance has limited their clinical activity. We report the synthesis and biological properties of a series of novel 3‐ch
Synthesis, biochemical and molecular modelling studies of antiproliferative azetidinones causing microtubule disruption and mitotic catastrophe
O'Boyle, Niamh M.,Carr, Miriam,Greene, Lisa M.,Keely, Niall O.,Knox, Andrew J.S.,McCabe, Thomas,Lloyd, David G.,Zisterer, Daniela M.,Meegan, Mary J.
experimental part, p. 4595 - 4607 (2011/11/04)
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
