Understanding the functional mechanism of ipomoeassin natural glycoresins.

by Shi, Wei; Zong, Guanghui; Hu, Zhijian; Aljewari, Hazim; Zhou, Jianhong; Du, Yuchun

Bioactive natural products are a rich source of drug candidates as well as important tools for investigating biol. systems. Ipomoeassin F is a flagship congener of a plant-derived macrolide resin glycoside family with an embedded disaccharide core. It possesses potent cell growth inhibition activity with IC50 values in the single-digit nanomolar range. In the NCI 60-cell line screen, ipomoeassin A---a structural homolog of ipomoeassin F---demonstrated a unique cytotoxicity profile; however, its mode of action remains largely unexplored. We recently accomplished the gram-scale prodn. of ipomoessin F and have been carrying out systematic studies to understand its structure-activity relationship. To further harness scientific values of this special chem. space, we report here the first studies towards target deconvolution of ipomoeassin F using cell imaging and proteomics. This work represents a significant step forward in moving the ipomoeassin family of glycolipids into the field of chem. biol. for drug discovery.