Antiproliferative and pro-apoptotic activities of 2 '- and 4 '-aminochalcones against tumor canine cells

Autor(es)

Santos, Mariana B. ; Pinhanelli, Vitor C. ; Garcia, Mayara A. R. ; Silva, Gabriel ; Baek, Seung J. ; Franca, Suzelei C. ; Fachin, Ana L. ; Marins, Mozart ; Regasini, Luis O.

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY; v. 138, p. 6-pg., 2017-09-29.

Resumo

In the present study, a series of 2'- and 4'-aminochalcones were synthesized and their antiproliferative activity against a canine malignant histiocytic cell line (DH82) was evaluated. Particularly aminochalcones with a hydrophobic substituent on ring B proved to be potent antiproliferative agents. Among these compounds, aminochalcones 3, 4 and 11 inhibited the growth of DH82 cells, with IC50 values of 34.4, 31.4 and 38.2 mu M, respectively, and were three times more potent than etoposide (IC50 = 95.5 mu M). The selected chalcones induced death through apoptosis rather than necrosis in DH82 and non-tumorigenic Madin-Darby canine kidney cells (MDCK). Further experiments suggested that the aminochalcones interfere with the regulation of oncogenesitumor suppressor genes. Aminochalcone 11 inhibited transcription of the TOP011 alpha and TP53 genes and aminochalcone 4 down-regulated Sp1 protein expression in a concentration-dependent manner. (C) 2017 Elsevier Masson SAS. All rights reserved. (AU)

• Processo FAPESP: 14/15307-7 - Análise molecular da resposta de linhagens tumorais humanas e caninas ao flavonóide trans-chalcona
• Beneficiário: Mozart de Azevedo Marins
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/18330-0 - Preparação e avaliação biológica de híbridos curcumina-cinamaldeído como inibidores da divisão celular bacteriana
• Beneficiário: Luis Octávio Regasini
• Modalidade de apoio: Auxílio à Pesquisa - Regular