Diphyllin glycosides have recently garnered significant interest for their antiproliferative properties. A particularly potent member of this class, phyllanthusmin D, served as inspiration for lead optimization. After the synthesis of over 60 analogues, PHY-34 stood out as a novel lead compound displaying a 500-fold improvement in <i>in vitro</i> activity over phyllanthusmin D. PHY-34 also showed promising<i> in vivo</i> efficacy and late stage autophagy inhibition and hinted at potential oral bioavailability (2.5%). To further improve pharmacological properties, efficient routes to several late stage intermediates have been developed to investigate both the glycone and aglycone portions of the molecule as well as to develop a series of carbasugar analogues. The current hypotheses regarding mechanistic target(s) for this class of molecules, acquired through the synthesis of a variety of mechanistic probes, will also be discussed.

Novel phyllanthusmin derivatives as anticancer agents: Pharmaceutical optimization and mechanistic insight

2019 Fall National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.