Synthesis of luffariellolide derivatives and evaluation their anticancer activities

Abstract

Luffariellolide was isolated from the marine sponge Suberea sp. in a large quantity (> 300 mg). We conducted modification of the γ-hydroxybutenolide core of luffariellolide to synthesize 13 derivatives, using readily available nucleophiles. As a result, some of the pyridazinone analogues were exhibited increased anticancer activities against A375SM (melanonma). Especially, the synthetic derivative, bearing 2-(pyridin-2-yl) pyridazinone, exhibited almost four times higher anticancer activity (IC50 = 6.35 μM) compared to that of luffariellolide (IC50 = 24.4 μM).. As a result, some of the pyridazinone analogues were exhibited increased anticancer activities against A375SM (melanonma). Especially, the synthetic derivative, bearing 2-(pyridin-2-yl) pyridazinone, exhibited almost four times higher anticancer activity (IC50 = 6.35 μM) compared to that of luffariellolide (IC50 = 24.4 μM).