Synthesis and biological evaluation of coumarin derivatives as selective CYP2A6 inhibitors.

ID: ALA5252607

Journal: Bioorg Med Chem Lett

Title: Synthesis and biological evaluation of coumarin derivatives as selective CYP2A6 inhibitors.

Authors: Yamaguchi Y, Nishizono N, Kobayashi D, Yoshimura T, Wada K, Kobayashi K, Oda K.

Abstract: Cytochrome P450 2A6 (CYP2A6) inhibitors are expected to be suitable as smoking cessation aids and for cancer prevention. Because the typical coumarin-based CYP2A6 inhibitor methoxsalen also inhibits CYP3A4, unintended drug-drug interactions are still a concern. Therefore, the development of selective CYP2A6 inhibitors is desirable. In this study, we synthesized coumarin-based molecules, determined the IC₅₀ values for CYP2A6 inhibition, verified the possibility of mechanism-based inhibition, and compared the selectivity for CYP2A6 versus CYP3A4. The results demonstrated that we developed CYP2A6 inhibitors that were more potent and selective than methoxsalen.

CiteXplore: 36889653

DOI: 10.1016/j.bmcl.2023.129206

Patent ID: ┄