Chemical Synthesis and Biological Evaluation of Second-Generation Palmerolide A Analogues

In this communication, second-generation analogues of palmerolide A, a recently reported cytotoxic agent against melanoma cancer cells, were rationally designed, synthesized, and biologically evaluated. Structural variations of the enamide side chain and the C1-C8 segment of palmerolide A revealed a narrow structure-activity relationship window of the newly synthesized compounds. In addition, mechanistic and pharmacological studies were performed to assess the therapeutic potential of palmerolide A.