title: 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.affiliation: Organic Chemistry Laboratory, University of Bayreuth, Universitaetsstrasse 30, 95440 Bayreuth, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Biersack
authors.forename: Katharina
authors.initials: K
authors.lastname: Effenberger
authors.forename: Rainer
authors.initials: R
authors.lastname: Schobert
authors.forename: Matthias
authors.initials: M
authors.lastname: Ocker
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D029765:Combretum / Q000737:chemistry; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D045325:HCT116 Cells; D018922:HL-60 Cells; D019073:HT29 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010080:Oxazoles / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D050759:Cyclin-Dependent Kinase Inhibitor p21; D010080:Oxazoles; D017382:Reactive Oxygen Species; D013267:Stilbenes; D016159:Tumor Suppressor Protein p53; C058728:fosbretabulin