Synthesis and PI3 Kinase Inhibition Activity of a Wortmannin-Leucine Derivative.

Wortmannin is a potent covalent inhibitor of PI3K that shows substantial in vivo toxicity and thus is unsuitable for systemic therapeutic applications. One possible approach to minimize systemic toxicity is to generate a latent wortmannin pro-drug that will be selectively activated in target tissues. To test this approach, a wortmannin derivative with a leucine linker attached to C20 has been synthesized and tested for inhibition of PI3K activity in prostate cancer cells.