Document Detail


Aroyl hydrazones of 2-phenylindole-3-carbaldehydes as novel antimitotic agents.
MedLine Citation:
PMID:  18513974     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cell cycle arrest of malignant cells is an important option for cancer treatment. In this study, we modified the structure of antimitotic 2-phenylindole-3-carbaldehydes by condensation with hydrazides of various benzoic and pyridine carboxylic acids. The resulting hydrazones inhibited the growth of MDA-MB 231 and MCF-7 breast cancer cells with IC(50) values of 20-30 nM for the most potent derivatives. These 2-phenylindole derivatives also exerted an inhibitory effect on the growth of both proliferating and resting U-373 MG glioblastoma cells. Though the hydrazones exhibited similar structure-activity relationships as the aldehydes, they did not inhibit tubulin polymerization as the aldehydes but were capable of blocking the cell cycle in G(2)/M phase. The cell cycle arrest was accompanied by apoptosis as demonstrated by the activation of caspase-3. Since these 2-phenylindole-based hydrazones display no structural similarity with other antitumor drugs they are interesting candidates for further development.
Authors:
Susanne Vogel; Doris Kaufmann; Michaela Pojarová; Christine Müller; Tobias Pfaller; Sybille Kühne; Patrick J Bednarski; Erwin von Angerer
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Publication Detail:
Type:  Journal Article     Date:  2008-05-03
Journal Detail:
Title:  Bioorganic & medicinal chemistry     Volume:  16     ISSN:  1464-3391     ISO Abbreviation:  Bioorg. Med. Chem.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-06-13     Completed Date:  2008-07-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9413298     Medline TA:  Bioorg Med Chem     Country:  England    
Other Details:
Languages:  eng     Pagination:  6436-47     Citation Subset:  IM    
Affiliation:
Institut für Pharmazie, Universität Regensburg, D-93040 Regensburg, Germany.
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MeSH Terms
Descriptor/Qualifier:
Antimitotic Agents / chemical synthesis,  chemistry*,  pharmacology*
Benzoic Acids / chemistry
Caspase 3 / metabolism
Cell Cycle / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects*
Humans
Hydrazones / chemical synthesis,  chemistry*,  pharmacology*
Indoles / chemistry*
Pyridines / chemistry
Chemical
Reg. No./Substance:
0/Antimitotic Agents; 0/Benzoic Acids; 0/Hydrazones; 0/Indoles; 0/Pyridines; EC 3.4.22.-/Caspase 3

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


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