Design and synthesis of 4-acetoxypentanamide derivatives of spliceostatin A and their biological evaluation towards prostate cancer treatment

We designed and synthesized novel 4-acetoxypentanamide derivatives of spliceostatin A, whose 4-acetoxypente-namide moiety is reduced (7), isomerized (8), or substituted with methyl at the & alpha;-position (9). The results of biological evaluation against AR-V7 and the docking analysis of each derivative suggest that the geometry of the 4-acetoxypentenamide moiety of spliceostatin A is important for its biological activity.

Automated summary

We designed and synthesized novel derivatives of spliceostatin A with modified 4-acetoxypentanamide moiety through reduction (7), isomerization (8), or substitution with methyl at the α-position (9). The biological evaluation and docking analysis of each derivative indicate that the geometric configuration of the 4-acetoxypentenamide moiety of spliceostatin A is crucial for its biological activity.