Oxazole-bridged combretastatin A analogues with improved anticancer properties.

Abstract

Three new oxazole-bridged combretastatin A analogues with additional functional groups at the B-ring [-SMe, -OH, p-quinone] were tested for antiproliferative activity and specificity on human HL-60 leukemia, 518A2 melanoma, and colon carcinomas HCT-116 (wt)/(p53(-/-)) and HT-29 cells. While all oxazoles, except quinone 8, were efficacious against HCT-116 cells at submicromolar IC(50) values (48 h incubation), only thioanisole 5 achieved this potency in combretastatin-refractory HT-29 cells by significant upregulation of p21(cip1/waf1) associated with an S/G(2) cell-cycle arrest.

• Authors: Bernhard Biersack, Katharina Effenberger, Rainer Schobert, Matthias Ocker
• Journal: ChemMedChem (ChemMedChem) Vol. 5 Issue 3 Pg. 420-7 (Mar 01 2010) ISSN: 1860-7187 [Electronic] Germany
• PMID: 20112324 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Cyclin-Dependent Kinase Inhibitor p21
• Oxazoles
• Reactive Oxygen Species
• Stilbenes
• Tumor Suppressor Protein p53
• fosbretabulin

Topics

• Antineoplastic Agents, Phytogenic (chemical synthesis, chemistry, pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Combretum (chemistry)
• Cyclin-Dependent Kinase Inhibitor p21 (genetics)
• Gene Expression Regulation, Neoplastic (drug effects)
• HCT116 Cells
• HL-60 Cells
• HT29 Cells
• Humans
• Membrane Potential, Mitochondrial (drug effects)
• Oxazoles (chemistry)
• Reactive Oxygen Species (metabolism)
• Stilbenes (chemical synthesis, chemistry, pharmacology)
• Tumor Suppressor Protein p53 (genetics)