(<i>S</i>)‑<i>N</i>‑Methyldihydroquinazolinones are the Active Enantiomers of Retro‑2 Derived Compounds against Toxins

This study reports the synthesis, chromatographic separation, and pharmacological evaluation of the two enantiomers of a new compound, named Retro-2.1, active against toxins by inhibiting intracellular trafficking via the retrograde route. The absolute configuration of the bioactive enantiomer has been assigned from X-ray diffraction to the (<i>S</i>)-enantiomer. To date, (<i>S</i>)-Retro-2.1 is the most potent molecule to counteract the cytotoxic potential of ricin and Shiga toxin, with EC50 values of 23 and 54 nM, respectively