Metabolism of pyrrolizidine alkaloids (PAs) generates dehydro-PA(pyrrolic) metabolites which exert hepatoxicity and genotoxicity, including tumorigenicity. However, reaction of dehydro-PAs with cellular constituents, such as amino acids, proteins, nucleic acids, and DNA, has not been systematically studied. We report the reactions of dehydroriddelliine, dehydromonocrotaline, and dehydrohehiotrine, with valine and hemoglobin. The products were derivatized with phenylisothiocyanate, and upon HPLC purification, the resulting products were characterized by mass, UV-visible, and 1H NMR spectral analysis. It was found that the reaction products were formed by linking the terminal amino group of valine and hemoglobin to the C7 and C9 positions of the necine base of dehydro-PAs. This represents the first full structure elucidation of protein conjugated pyrrolic adducts formed by linking the amino group of the amino acid to the necine base of dehydro-PAs (No official support or endorsement of this article by the U.S. FDA is intended or should be inferred.

Reactions of dehydropyrrolizidine alkaloids with valine and hemoglobin

244th National Meeting (2012)

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