Biblioteca Digital do Instituto Politécnico de Bragança   Instituto Politécnico de Bragança

Biblioteca Digital do IPB >
Escola Superior Agrária >
Biologia e Biotecnologia >
BB - Artigos em Revistas Indexados ao ISI >

Please use this identifier to cite or link to this item: http://hdl.handle.net/10198/6469

Título: Anti-hepatocellular carcinoma activity using human HepG2 cells and hepatotoxicity of 6-substituted methyl 3-aminothieno[3,2-b]pyridine-2- carboxylate derivatives: In vitro evaluation, cell cycle analysis and QSAR studies
Autor: Abreu, Rui M.V.
Ferreira, Isabel C.F.R.
Calhelha, Ricardo C.
Lima, Raquel T.
Vasconcelos, M. Helena
Adega, Filomena
Chaves, Raquel
Queiroz, Maria João R.P.
Palavras-chave: Thieno[3,2-b]pyridines
Anti-hepatocellular carcinoma activity
Hepatotoxicity
Cell cycle
QSAR studies
Issue Date: 2011
Editora: Elsevier
Citação: Abreu, Rui M.V.; Ferreira, Isabel C. F. R.; Calhelha, Ricardo C.; Lima, Raquel T.; Vasconcelos, M. Helena; Adega, Filomenna; Chaves, Raquel; Queiroz, Maria-João R. P. (2011) - Anti-hepatocellular carcinoma activity using human HepG2 cells and hepatotoxicity of 6-substituted methyl 3-aminothieno[3,2-b]pyridine-2- carboxylate derivatives: In vitro evaluation, cell cycle analysis and QSAR studies. European Journal of Medicinal Chemistry. ISSN 1768-3254. 46:12, p. 5800-5086
Resumo: Hepatocellular carcinoma (HCC) is a highly complex cancer, resistant to commonly used treatments and new therapeutic agents are urgently needed. A total of thirty-two thieno[3,2-b]pyridine derivatives of two series: methyl 3-amino- -(hetero)arylthieno[3,2-b]pyridine-2-carboxylates (1ae1t) and methyl 3-amino-6-[(hetero)arylethynyl]thieno[3,2-b]pyridine-2-carboxylates (2ae2n), previously prepared by some of us, were evaluated as new potential anti-HCC agents by studying their in vitro cell growth inhibition on human HepG2 cells and hepatotoxicity using a porcine liver primary cell culture (PLP1). The presence of amino groups linked to a benzene moiety emerges as the key element for the anti-HCC activity. The methyl 3-amino-6-[(3-aminophenyl)ethynyl]thieno[3,2-b]pyridine-2-carboxylate (2f) is the most potent compound presenting GI50 values on HepG2 cells of 1.2 mM compared to 2.9 mM of the positive control ellipticine, with no observed hepatotoxicity (PLP1 GI50 > 125 mM against 3.3 mM of ellipticine). Moreover this compound changes the cell cycle profile of the HepG2 cells, causing a decrease in the % of cells in the S phase and a cell cycle arrest in the G2/M phase. QSAR studies were also performed and the correlations obtained using molecular and 1D descriptors revealed the importance of the presence of amino groups and hydrogen bond donors for anti-HCC activity, and hydrogen bond acceptors for hepatotoxicity. The best correlations were obtained with 3D descriptors belonging to different subcategories for anti-HCC activity and hepatotoxicity, respectively. These results point to different molecular mechanisms of action of the compounds in anti-HCC activity and hepatotoxicity. This work presents some promising thieno[3,2-b]pyridine derivatives for potential use in the therapy of HCC. These compounds can also be used as scaffolds for further synthesis of more potent analogs.
Arbitragem científica: yes
URI: http://hdl.handle.net/10198/6469
ISSN: 1768-3254
Appears in Collections:BB - Artigos em Revistas Indexados ao ISI

Files in This Item:

File Description SizeFormat
EJMC-MJQ011_R1.doc2,95 MBMicrosoft WordView/Open
Statistics
FacebookTwitterDeliciousLinkedInDiggGoogle BookmarksMySpaceOrkut
Formato BibTex mendeley Endnote Logotipo do DeGóis 

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

 


  © Instituto Politécnico de Bragança - Biblioteca Digital - Feedback - Statistics
  Estamos no RCAAP Governo Português separator Ministério da Educação e Ciência   Fundação para a Ciência e a Tecnologia

Financiado por:

POS_C UE