Interactions of rutaecarpine alkaloids with specific binding sites for 2,3,7,8-tetrachlorodibenzo-p-dioxin in rat liver

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Abstract
Rutaecarpine alkaloids have the capacity to inhibit specific 2,3,7,8-[1,6-3H]tetrachlorodibenzo-p-dioxin (TCDD) binding in rat liver cytosol, as analysed by electrofocusing in polyacrylamide gel. The IC50 value for binding of 7,8-dehydrorutaecarpine was estimated to ∼7 nM indicating a high-affinity interaction, whereas rutaecarpine appeared less active (IC50 ∼110 nM). These findings are of interest in view of the fact that analogues to these compounds may be formed following UV-irradiation of tryptophan and that such photo-products have been suggested to constitute (the) endogenous ligand(s) for the TCDD receptor. As further support of this notion, the rutaecarpine alkaloids investigated could be fitted into a rectangle of 6.8×13.7 A, a characteristic common for most high affinity ligands of the TCDD receptor hitherto studied. In view of their structural similarity to dehydrorutaecarpine and the agreement of their mol. wt with that of the photoproduct with the highest affinity for the TCDD receptor, we suggest deaza-analogues of dehydrorutaecarpine to represent possible candidates for the endogenous TCDD receptor ligand.