Document Detail

Synthesis and antitumor activity of 1,5-disubstituted 1,2,4-triazoles as cis-restricted combretastatin analogues.
MedLine Citation:
PMID:  20420439     Owner:  NLM     Status:  MEDLINE    
A series of 1-aryl-5-(3',4',5'-trimethoxyphenyl) derivatives and their related 1-(3',4',5'-trimethoxyphenyl)-5-aryl-1,2,4-triazoles, designed as cis-restricted combretastatin analogues, were synthesized and evaluated for antiproliferative activity, inhibitory effects on tubulin polymerization, cell cycle effects, and apoptosis induction. Their activity was greater than, or comparable with, that of the reference compound CA-4. Flow cytometry studies showed that HeLa and Jurkat cells treated with the most active compounds 4l and 4o were arrested in the G2/M phase of the cell cycle in a concentration dependent manner. This effect was accompanied by apoptosis of the cells, mitochondrial depolarization, generation of reactive oxygen species, activation of caspase-3, and PARP cleavage. Compound 4l was also shown to have potential antivascular activity, since it induced endothelial cell shape change in vitro and disrupted the sprouting of endothelial cells in the chick aortic ring assay.
Romeo Romagnoli; Pier Giovanni Baraldi; Olga Cruz-Lopez; Carlota Lopez Cara; Maria Dora Carrion; Andrea Brancale; Ernest Hamel; Longchuan Chen; Roberta Bortolozzi; Giuseppe Basso; Giampietro Viola
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  53     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-20     Completed Date:  2010-06-22     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4248-58     Citation Subset:  IM    
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Ferrara, Italy.
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MeSH Terms
Angiogenesis Inhibitors / chemical synthesis,  chemistry,  pharmacology
Antineoplastic Agents / chemical synthesis*,  chemistry,  pharmacology
Bibenzyls / chemical synthesis*,  chemistry,  pharmacology
Caspase 3 / metabolism
Cell Line, Tumor
Cell Shape
Cells, Cultured
Chick Embryo
Colchicine / chemistry
Drug Screening Assays, Antitumor
Endothelial Cells / cytology,  drug effects,  physiology
Enzyme Activation
G2 Phase / drug effects
Membrane Potential, Mitochondrial / drug effects
Mitochondria / drug effects,  physiology
Models, Molecular
Poly(ADP-ribose) Polymerases / metabolism
Protein Binding
Proto-Oncogene Proteins c-bcl-2 / biosynthesis
Reactive Oxygen Species / metabolism
Structure-Activity Relationship
Triazoles / chemical synthesis*,  chemistry,  pharmacology
Tubulin / chemistry
Tubulin Modulators / chemical synthesis,  chemistry,  pharmacology
Grant Support
Reg. No./Substance:
0/1-(3,4,5-trimethoxyphenyl)-5-(4-ethoxyphenyl)-1H-1,2,4-triazole; 0/5-(3-Chloro-4-ethoxyphenyl)-1-(3,4,5-trimethoxyphenyl)-1H-1,2,4-triazole; 0/Angiogenesis Inhibitors; 0/Antineoplastic Agents; 0/Bibenzyls; 0/Proto-Oncogene Proteins c-bcl-2; 0/Reactive Oxygen Species; 0/Triazoles; 0/Tubulin; 0/Tubulin Modulators; 64-86-8/Colchicine; 82855-09-2/combretastatin; EC Polymerases; EC 3.4.22.-/Caspase 3

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

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