Document Detail


Efficient synthesis and biological evaluation of demethyl geranylgeranoic acid derivatives.
MedLine Citation:
PMID:  20673632     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Synthetic retinoids have generated in the fields of dermatology and oncology due to their potent anti-proliferative and differentiation activities. We efficiently synthesized different demethyl geranylgeranoic acid (GGA) analogs, and evaluated their biological activities. Among the demethyl analogs synthesized, 3-demethyl derivative exhibited the highest anti-proliferative activity in HL-60 cells. In addition, a 3-demethyl derivative induced apoptosis more potently than 9Z-retinoic acid. These activities were due to the high binding affinity of 3-demethyl derivative for retinoid receptors. We found that, in a conjugated polyene system combined with a methyl substituent, the position of the methyl played an important role in the regulation of gene transcription and apoptosis-inducing activity. These results provided useful information on the structure-activity relationships of GGA derivatives that function as acyclic retinoic acid analogs. This information is likely to be useful in the development of new anti-cancer drugs.
Authors:
Akimori Wada; Fei Wang; Yoshitomo Suhara; Yumiko Yamano; Takashi Okitsu; Kimie Nakagawa; Toshio Okano
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-08
Journal Detail:
Title:  Bioorganic & medicinal chemistry     Volume:  18     ISSN:  1464-3391     ISO Abbreviation:  Bioorg. Med. Chem.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-09     Completed Date:  2010-12-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9413298     Medline TA:  Bioorg Med Chem     Country:  England    
Other Details:
Languages:  eng     Pagination:  5795-806     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Organic Chemistry for Life Science, Kobe Pharmaceutical University, Higashinada-ku, Kobe, Japan. a-wada@kobepharma-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects*
Cell Line, Tumor
Diterpenes / chemical synthesis,  chemistry*,  pharmacology*
HL-60 Cells
Humans
Methylation
Rats
Retinoid X Receptors / genetics
Transcriptional Activation / drug effects
Tretinoin / analogs & derivatives,  pharmacology
Chemical
Reg. No./Substance:
0/Diterpenes; 0/Retinoid X Receptors; 302-79-4/Tretinoin; 83807-40-3/geranylgeranic acid

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