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

Abstract 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 IC 50 values of 34.4, 31.4 and 38.2 μM, respectively, and were three times more potent than etoposide (IC 50  = 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.