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

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Data

2017-01-01

Autores

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

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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 μM, respectively, and were three times more potent than etoposide (IC50 = 95.5 μM). 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 oncogenes/tumor suppressor genes. Aminochalcone 11 inhibited transcription of the TOPOIIα and TP53 genes and aminochalcone 4 down-regulated Sp1 protein expression in a concentration-dependent manner.

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Palavras-chave

Antiproliferative, Apoptosis, Canine cancer, Chalcone

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European Journal of Medicinal Chemistry, v. 138, p. 884-889.