Synthesis and SERCA activities of structurally simplified cyclopiazonic acid analogues

The indole alkaloid cyclopiazonic acid (CPA) is one of the few known nanomolar inhibitors of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) besides the anticancer drug thapsigargin and the antiplasmoidal terpenoid artemisinin. Due to its less complex structure CPA represents an attractive lead structure for the development of novel antimalarial drugs or for applications in the field of plant protection. We report here the first syntheses of structurally simplified CPA fragments and discuss their SERCA activities on the basis of published crystal structures of CPA–SERCA complexes.

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