Synthesis and anti-proliferative activity of novel azazerumbone conjugates with chalcones

The conjugation of azazerumbone ((3E, 7E, 11E)-5,5,8,12-tetramethylazacyclododeca-3,7,11-trien-2-one (7)) and 2,4-dihydroxychalcones was carried out for the preparation of novel target compounds 9a-g with 1-ethylene-4-methylene-1,2,3-triazole linker and 10a-f with propylene linker between amide nitrogen of azazerumbone and 4-hydroxy group of chalcone. The anti-proliferative activity of these compounds against the LU-1, Hep-G2, MCF-7 and SW480 human cancer cell lines were significantly improved compared to those of azazerumbone or zerumbone. The anti-proliferative activities of (3E, 7E, 11E)-1-((1-(2-(3-hydroxy-4-((E)-3-(3-methoxyphenyl) acryloyl) phenoxy) ethyl)-1H-1,2,3-triazol-4-yl) methyl)-5,5,8,12-tetramethyl azacyclododeca-3,7,11-trien-2-one (9b) and (3E, 7E, 11E)-1-(3-(4-((E)-3-(3,4,5-trimethoxyphenyl) acryloyl) phenoxy) propyl)-5,5,8,12-tetramethylazacyclododeca- 3,7,11-trien-2-one (10d) are nearly comparable to those of ellipticine. (C) 2015 Elsevier Ltd. All rights reserved.