Quaternary Isoquinoline Alkaloids Sanguinarine and Chelerythrine. In vitro and in vivo Effects

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A. Zdařilováa, J. Malíkováb, Z. Dvořáka, J. Ulrichováa, and V. Šimáneka

aInstitute of Medicinal Chemistry and Biochemistry, bInstitute of Pathology, Faculty of Medicine, Palacký University, Olomouc


Quaternary benzo[c]phenanthridine alkaloids (QBA) sanguinarine (SA) and chelerythrine (CHE) are found within the families Fumariaceae, Papaveraceae, Ranunculaceae and Rutaceae. These alkaloids originate from aromatic amino acids tyrosine and phenylalanine. Important intermediates in their biosynthesis are protopines; its last step is the oxidation of dihydro-QBA to QBA with benzo[c]phenanthridine oxidase. The strong antimicrobial activity of QBA suggests their function as plant defense secondary metabolites or phytoalexins. If these alkaloids are administered to living organisms such as insects, fish, and mammalian species, they can be absorbed, distributed, retained and/or metabolized as quaternary ammonium compounds, 6-hydroxy dihydro derivatives (pseudobases) and/or dihydro derivatives. In blood and organs, the equilibrium between these forms depends mainly on pH, ionic strength and oxidative capacity of the medium. Their resulting mode of action reflects the sum of reactions of all three chemical structures with cellular components. The formation of dihydro-QBA might be the first step of their detoxication in organism and their subsequent elimination. Benzo[c]acridine is not a metabolite of QBA in mammals. This review presents the resulting biological effects of QBA on cells and animals.


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