Document Detail


Synthesis and in vitro and in vivo antitumor activity of 2-phenylpyrroloquinolin-4-ones.
MedLine Citation:
PMID:  15857148     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In our search for potential new anticancer drugs, we designed and synthesized a series of tricyclic compounds containing the antimitotic 2-phenylazaflavone chromophore fused to a pyrrole ring in a pyrroloquinoline structure. Compounds 8, 18, 19, 22, 23, 25 and 26, when tested against a panel of fourteen human tumor cell lines, showed poor in vitro cytotoxic activity, whereas 20, 21 and 24 showed significant activity (IC(50) 0.7 to 50 microM). Steroid hormone-sensitive ovary, liver, breast and adrenal gland adenocarcinoma cell lines displayed the highest sensitivity (IC(50) 0.7 to 8 microM). Compound 24 blocked cells in the G(2)/M phase of the cell cycle and induced a significant increase in apoptotis. Compounds 20, 21 and 24 proved to alter microtubule assembly and stability, displaying a cytoplasmic microtubule network similar to that caused by Vincristine. In vivo, administration of compound 24 to Balb/c mice inhibited the growth of a syngenic hepatocellular carcinoma.
Authors:
Maria Grazia Ferlin; Gianfranco Chiarelotto; Venusia Gasparotto; Lisa Dalla Via; Vincenzo Pezzi; Luisa Barzon; Giorgio Palù; Ignazio Castagliuolo
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  48     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-04-28     Completed Date:  2005-06-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3417-27     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutical Sciences, and Department of Histology, Microbiology and Medical Biotechnologies, University of Padova, Italy. mariagrazia.ferlin@ unipd.it
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / chemical synthesis*,  chemistry,  pharmacology
Apoptosis
Aromatase Inhibitors / chemical synthesis,  chemistry,  pharmacology
Carcinoma, Hepatocellular / drug therapy
Cell Cycle / drug effects
Cell Line, Tumor
DNA Topoisomerases, Type I / antagonists & inhibitors
DNA Topoisomerases, Type II / antagonists & inhibitors
Drug Screening Assays, Antitumor
Humans
Liver Neoplasms / drug therapy
Male
Mice
Mice, Inbred BALB C
Microtubules / drug effects,  ultrastructure
Neoplasm Transplantation
Neoplasms, Hormone-Dependent
Pyrroles / chemical synthesis*,  chemistry,  pharmacology
Quinolines / chemical synthesis*,  chemistry,  pharmacology
Structure-Activity Relationship
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Aromatase Inhibitors; 0/Pyrroles; 0/Quinolines; EC 5.99.1.2/DNA Topoisomerases, Type I; EC 5.99.1.3/DNA Topoisomerases, Type II

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