Preparation and biological evaluation of phosphoryl and phosphonyl derivatives of goniothalamin and piplartine

Abstract

The biological relevance of biomolecules prone to undergo phosphorylation and dephosphorylation processes is associated to their ability to control the biological role of kinase and phosphatase proteins. Several phosphorylated or phosphonylated organic compounds act as inhibitors or chemical probes for the aforementioned enzymes. This research proposal aims the preparation of phosphoryl, phosphonyl and phosphonoamidate analogues of the natural products goniothalamin and piplartine using direct (activation by trichloroacetonitrile, enol pyruvate phosphate, aryl and allyl phosphoramidites) as well as electrochemical methods. The natural products goniothalamin and piplartine are known for their cytotoxic action on several Cancer cell lines and the targeted analogues will be screened against Breast Cancer (MCF-7 and MDA-MB-231), prostate (PC-3) and normal prostate (PNT2) cell lines. (AU)