The enone motif of (+)-grandifloracin is not essential for ‘anti-austerity’ antiproliferative activity

Abstract

We report the synthesis and biological evaluation of three analogues of the natural product (+)-grandifloracin (+)-1. All three analogues exhibit enhanced antiproliferative activity against PANC-1 and HT-29 cells compared to the natural product. The retention of activity in an analogue lacking the enone functional group, 9, implies this structural element is not an essential part of the (+)-grandifloracin pharmacophore.

Exceedingly Efficient Synthesis of (±)-Grandifloracin and Acylated Analogues

“…In summary, we have completed a highly efficient synthesis of (±)-grandifloracin, which is amenable to late-stage diversification for the synthesis of analogues. In a recent study, analogue 7d has been shown to have an increased antiproliferative effect compared with grandifloracin on PANC-1 and HT-29 (human colon cancer) cells, both in nutrient-rich (10% fetal bovine serum) and in nutrient-deprived conditions (0.5% fetal bovine serum) . This indicates that there is an incentive to develop further grandifloracin analogues for the study and treatment of pancreatic cancer.…”