PDE-I2 is a potent and selective inhibitor of malaria proliferation with P. falciparum IC50 of 18 nM.
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.
PDE-I2 retains comparable antimalarial potency to chloroquine.
PDE-I2 is >1,000-fold less toxic to human cell lines than duocarmycin, with mitigated impacts on eukaryotic chromosome stability.
PDE-I2 treatment induces severe defects in parasite nuclear segregation leading to impaired daughter cell formation during schizogony.
