Document Detail

Evaluation of the mutagenic/clastogenic potential of 3,6-di-substituted acridines targeted for anticancer chemotherapy.
MedLine Citation:
PMID:  21802476     Owner:  NLM     Status:  Publisher    
The mutagenicity and clastogenicity of a series of 18 3,6-di-substituted acridines were evaluated by the Ames test on Salmonella typhimurium TA 97a and by the micronucleus assay on Chinese Hamster Ovary cells (CHO cells), as compared to their cytotoxicity against CHO cells. Experimental results overall demonstrated that simple symmetric molecules were more mutagenic than asymmetric structures. The mutagenic properties of acridines on strain TA97a mainly depended on molecular geometry and length, and on the nature of the substituted groups. The clastogenicity of acridines mainly depended on molecular length and electrophilicity in mammalian cells. Structure-activity relationships indicated that cytotoxicity could be decoupled from genotoxicity by introducing several chemical groups that induced asymmetry or bulkiness in the acridine compounds. They led to the synthesis of the promising 3-acetamido-6-(4-fluorobenzamido)acridine, which displayed a strong cytotoxic activity and was not mutagenic.
Carole Di Giorgio; Yohann Benchabane; Gérard Boyer; Philippe Piccerelle; Michel De Méo
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-23
Journal Detail:
Title:  Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association     Volume:  -     ISSN:  1873-6351     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-8-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8207483     Medline TA:  Food Chem Toxicol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier Ltd.
Laboratoire de Biogénotoxicologie et Mutagenèse Environnementale (EA 1784, FR 3098 - ECCOREV), Université Aix-Marseille, Faculté de Pharmacie, 27 Bd Jean Moulin, 13385 Marseille Cedex 05, France.
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