Abstract
Ipomoeassin F, the flagship congener of a resin glycoside family exhibited single-digit nanomolar IC50 values against several cancer cell lines. To facilitate drug discovery based on this unique yet underexplored natural product, we performed the most sophisticated SAR studies of ipomoeassin F to date, which not only greatly bettered our understanding of its pharmacophore but also led to the discovery of two new derivatives (3 and 27) with similar potency but improved synthetic profile. The work presented here opens new avenues toward harnessing the medicinal potential of the ipomoeassin family of glycolipids in the future.
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