Document Detail

Synthesis and biological evaluation of 2-(alkoxycarbonyl)-3-anilinobenzo[b]thiophenes and thieno[2,3-b]pyridines as new potent anticancer agents.
MedLine Citation:
PMID:  23445496     Owner:  NLM     Status:  MEDLINE    
Two new series of inhibitors of tubulin polymerization based on the 2-(alkoxycarbonyl)-3-(3',4',5'-trimethoxyanilino)benzo[b]thiophene and thieno[2,3-b]pyridine molecular skeletons were synthesized and evaluated for antiproliferative activity on a panel of cancer cell lines, inhibition of tubulin polymerization, cell cycle effects, and in vivo potency. Antiproliferative activity was strongly dependent on the position of the methyl group on the benzene portion of the benzo[b]thiophene nucleus, with the greatest activity observed when the methyl was located at the C-6 position. Also, in the smaller thieno[2,3-b]pyridine series, the introduction of the methyl group at the C-6 position resulted in improvement of antiproliferative activity to the nanomolar level. The most active compounds (4i and 4n) did not induce cell death in normal human lymphocytes, suggesting that the compounds may be selective against cancer cells. Compound 4i significantly inhibited in vivo the growth of a syngeneic hepatocellular carcinoma in Balb/c mice.
Romeo Romagnoli; Pier Giovanni Baraldi; Maria Kimatrai Salvador; Delia Preti; Mojgan Aghazadeh Tabrizi; Marcella Bassetto; Andrea Brancale; Ernest Hamel; Ignazio Castagliuolo; Roberta Bortolozzi; Giuseppe Basso; Giampietro Viola
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Publication Detail:
Type:  Journal Article     Date:  2013-03-18
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  56     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-28     Completed Date:  2013-05-23     Revised Date:  2014-03-31    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2606-18     Citation Subset:  IM    
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MeSH Terms
Antineoplastic Agents / chemical synthesis*,  chemistry,  pharmacology*,  toxicity
Apoptosis / drug effects
Apoptosis Regulatory Proteins / metabolism
Cell Cycle / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Chemistry Techniques, Synthetic
Colchicine / metabolism
Drug Resistance, Multiple / drug effects
Drug Resistance, Neoplasm / drug effects
Lymphocytes / drug effects
Mitochondria / drug effects,  pathology
Models, Molecular
P-Glycoproteins / metabolism
Protein Multimerization / drug effects
Protein Structure, Quaternary
Pyridines / chemical synthesis*,  chemistry,  pharmacology*,  toxicity
Thiophenes / chemical synthesis*,  chemistry,  pharmacology*,  toxicity
Tubulin / chemistry,  metabolism
Xenograft Model Antitumor Assays
Grant Support
Reg. No./Substance:
0/Antineoplastic Agents; 0/Apoptosis Regulatory Proteins; 0/P-Glycoproteins; 0/Pyridines; 0/Thiophenes; 0/Tubulin; SML2Y3J35T/Colchicine

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