A non-reactive natural product precursor of the duocarmycin family has potent and selective antimalarial activity

We identify a selective nanomolar inhibitor of blood-stage malarial proliferation from a screen of microbial natural product extracts. The responsible compound, PDE-I₂, is a precursor of the anticancer duocarmycin family that preserves the class's sequence-specific DNA binding but lacks its signature DNA alkylating cyclopropyl warhead. While less active than duocarmycin, PDE-I₂ retains comparable antimalarial potency to chloroquine. …