Synthesis enables identification of the cellular target of leucascandrolide A and neopeltolide.

ABSTRACT: Leucascandrolide A and neopeltolide are structurally homologous marine natural products that elicit potent antiproliferative profiles in mammalian cells and yeast. The scarcity of naturally available material has been a significant barrier to their biochemical and pharmacological evaluation. We developed practical synthetic access to this class of natural products that enabled the determination of their mechanism of action. We demonstrated effective cellular growth inhibition in yeast, which was substantially enhanced by substituting glucose with galactose or glycerol. These results, along with genetic analysis of determinants of drug sensitivity, suggested that leucascandrolide A and neopeltolide may inhibit mitochondrial ATP synthesis. Evaluation of the activity of the four mitochondrial

SUBMITTER: Ulanovskaya OA 

PROVIDER: S-EPMC2673112 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature