Effect of structural modification on the inhibitory selectivity of rutaecarpine derivatives on human CYP1A1, CYP1A2, and CYP1B1

Derivatives of a CYP1A2 inhibitor rutaecarpine were synthesized to have potent and selective inhibition of human CYP1 members. Structural modelling shows a good fitting of rutaecarpine with the putative active site of human CYP1A2. Among the derivatives, 10- and 11-methoxyrutaecarpine are the most selective CYP1B1 inhibitors. 1-Methoxyrutaecarpine and 1,2-dimethoxyrutaecarpine are the most selective CYP1A2 inhibitors.