Document Detail


4-(3-Halo/amino-4,5-dimethoxyphenyl)-5-aryloxazoles and -N-methylimidazoles that are cytotoxic against combretastatin A resistant tumor cells and vascular disrupting in a cisplatin resistant germ cell tumor model.
MedLine Citation:
PMID:  20731355     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
New combretastatin A analogues featuring oxazole or N-methylimidazole bridged Z-alkenes and halo- or amino-substituted A-rings were tested against various cancer cell lines and in testicular germ cell tumor xenografts in mice. Imidazoles with 3-halo-4,5-dimethoxy substituted A-rings and 3-amino-4-methoxy substituted B-rings (7b and 8b) were efficacious at nanomolar concentrations against cells of combretastatin A refractory HT-29 colon carcinoma, multidrug-resistant MCF-7/Topo breast carcinoma, and cisplatin-resistant 1411HP testicular germ cell tumor. They induced apoptosis and inhibited tubulin polymerization. While well tolerated by mice at high doses, these imidazoles initiated extensive intratumoral hemorrhage and regressions of highly vascularized 1411HP xenografts.
Authors:
Rainer Schobert; Bernhard Biersack; Andrea Dietrich; Katharina Effenberger; Sebastian Knauer; Thomas Mueller
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  53     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-16     Completed Date:  2010-10-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6595-602     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine IV, Oncology/Hematology, Martin Luther University Halle-Wittenberg, Ernst-Grube-Strasse 40, D-06120 Halle, Germany.
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MeSH Terms
Descriptor/Qualifier:
Angiogenesis Inhibitors / chemical synthesis,  chemistry,  pharmacology
Animals
Antineoplastic Agents / chemical synthesis*,  chemistry,  pharmacology
Cell Line, Tumor
Chick Embryo
Cisplatin / pharmacology*
Drug Resistance, Multiple
Drug Resistance, Neoplasm*
Drug Screening Assays, Antitumor
Humans
Imidazoles / chemical synthesis*,  chemistry,  pharmacology
Male
Mice
Mice, Nude
Neoplasm Transplantation
Neoplasms, Germ Cell and Embryonal / blood supply,  drug therapy*
Neovascularization, Pathologic / drug therapy
Neovascularization, Physiologic / drug effects
Oxazoles / chemical synthesis*,  chemistry,  pharmacology
Stilbenes / chemical synthesis*,  chemistry,  pharmacology
Structure-Activity Relationship
Testicular Neoplasms / blood supply,  drug therapy*
Transplantation, Heterologous
Tubulin Modulators / chemical synthesis,  chemistry,  pharmacology
Chemical
Reg. No./Substance:
0/1-methyl-5-(3''-amino-4''-methoxyphenyl)-4-(3'-chloro-4',5'-dimethoxyphenyl)imidazole; 0/Angiogenesis Inhibitors; 0/Antineoplastic Agents; 0/Imidazoles; 0/Oxazoles; 0/Stilbenes; 0/Tubulin Modulators; 117048-59-6/combretastatin A-4; 15663-27-1/Cisplatin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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