These novel antiproliferative and antiapoptotic β-lactams are potentially useful scaffolds in the development of tubulin-targeting agents for the treatment of breast cancers and chemoresistant colon cancers. In addition, compound 46 induced mitotic arrest at low concentration in both cell lines MCF-7 and HT-29 together with downregulation of expression of antiapoptotic proteins Mcl-1, Bcl-2 and survivin in MCF-7 cells. Compound 46 binds at the colchicine site of tubulin, and strongly inhibits tubulin assembly at micromolar concentrations comparable to CA-4. In Carbon Copy Cloner, you can backup either a whole drive or part of the drive to an external hard drive at a scheduled time of your choosing (hourly, daily, weekly, monthly, etc.).
The 3-phenyl-β-lactam 11 and 3-hydroxy-β-lactam 46 demonstrate improved activity over CA-4 in CA-4 resistant HT-29 colon cancer cells (IC 50 = 9 nM and 3 nM respectively compared with IC 50 = 4.16 μM for CA-4), while retaining potency in MCF-7 breast cancer cells (IC 50 = 17 nM and 22 nM respectively compared with IC 50 = for 4 nM for CA-4). Carbon Copy Cloner (CCC), is a Mac OS X application that can be used for creating file backups, complete images of your computer, or for cloning hard drives. Potential sites of ring B glucuronate conjugation are removed by replacing the B ring meta-hydroxy substituent of selected series of β-lactams with alternative substituents e.g. Glucuronidation of CA-4 by uridine 5-diphosphoglucuronosyl transferase enzymes (UGTs) has been identified as a mechanism of resistance in cancer cells.
A series of novel 1,4-diaryl-2-azetidinone analogues of combretastatin A-4 (CA-4) have been designed, synthesised and evaluated in vitro for antiproliferative activity, antiapoptotic activity and inhibition of tubulin polymerisation.
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