Cytotoxic natural product Ipomoeassin F: SAR-guided probe design for target identification

by Govindarajan, Mugunthan; Aljewari, Hazim; Zong, Guanghui; Shi, Wei

Ipomoeassins A-F are a family of resin glycosides isolated from the leaves of Ipomoea squamosa. In the NCI 60-cell line screen, Ipomoeassin A, the naturally most abundant member of the family, showed strong and selective growth inhibition of different cancer cells, and its pattern of activity was clearly distinguished from other known anticancer agents based on a COMPARE anal. This suggests that the ipomoeassin family of natural glycolipids acts through a unique and unknown mechanism of action, which needs to be identified. Ipomoeassin F was selected as our target mol. because it demonstrated the highest potency against cancer cell growth and holds the great potential of evolving to a successful lead. As a part of our ongoing efforts to identify the pharmacophore and hence a safe site for installing a probe moiety, this project aims at understanding the role of the Me group in the D-fucose. This was achieved by replacing the D-fucose moiety with L-Arabinose and D-Galactose residues. The primary hydroxyl group of D-galactose residue may facilitate incorporation of a probe moiety for target identification.