Synthesis and anti-tumor activity of EF24 analogues as IKKβ inhibitors

Role of the NFκB-signaling pathway in cancer

“… 139 As an IKKβ inhibitor, EF24 can block the NFκB-signaling pathway by inhibiting IKKβ phosphorylation, leading to cell-cycle arrest at the G 2 /M phase and apoptosis. 140 The proteasome inhibitor MG132 inhibits tumor growth through downregulation of the NFκB-signaling pathway. 141 , 142 In addition, T901 is a novel selective NFκB inhibitor functioning through binding to the NFκB complex in the cytosol, thus blocking its nuclear translocation and target-gene expression.…”

Properly Substituted Cyclic Bis-(2-bromobenzylidene) Compounds Behaved as Dual p300/CARM1 Inhibitors and Induced Apoptosis in Cancer Cells

“…The known 2,6-bis(( E )-2-bromobenzylidene)cyclohexan-1-one 4a [ 23 ], 3,5-bis(( E )-2-bromobenzylidene)tetrahydro-4 H -pyran-4-one 4b [ 24 ], 3,5-bis(( E )-2-bromobenzylidene)piperidin-4-one 4c [ 25 ], and 3,5-bis(( E )-2-bromobenzylidene)-1-methylpiperidin-4-one 4d [ 24 , 25 ] were prepared through aldol condensation between 2-bromobenzaldehyde and the appropriate 6-membered cyclic ketones by replacing sodium hydroxide, used as the basic catalyst in the previous reports [ 23 , 24 , 25 ], with barium hydroxide and methanol for 2 h at room temperature. Starting from 4c , compounds 4e – j were obtained by alkylation with suitable alkyl chlorides heating at 60 °C for 2 h in the presence of K 2 CO 3 in dry acetonitrile (MeCN) ( 4e – i ), or by one-pot reductive amination with 4-oxo-4-phenylbutanal and sodium triacetoxyborohydride [NaBH(AcO 3 ) 3 ] in dry dichloromethane (DCM) ( 4j ) for 2 h at room temperature ( Scheme 1 ).…”

“…3,5-Bis(( E )-2-bromobenzyliden)piperidin-4-one 4c [ 25 ] (0.46 mmol, 200 g, 1 eq.) and benzyl bromide (1.38 mmol, 164 µL, 3 eq.)…”

“…To a stirring solution of the 3,5-bis(( E )-2-bromobenzylidene)piperidin-4-one ( 4c ) [ 25 ] (0.46 mmol, 200 mg) and 4-oxo-4-phenylbutanal (0.46 mmol, 75 mg) in anhydrous dichloromethane (10 mL), sodium triacetoxyborohydride (0.55 mmol, 117 mg, 1.2 eq.) was added portion wise and the resulting suspension was stirred at room temperature.…”

“…Cinnamoyl chloride (0.67 mmol, 100 µL) was slowly added at 0 °C to a stirring solution of 4c [ 25 ] (0.45 mmol, 195 mg) and Et 3 N (0.76 mmol, 110 µL, 1.13 eq.) in anhydrous dichloromethane (5 mL).…”