Photosensitive Ru(II) Complexes as Inhibitors of the Major Human Drug Metabolizing Enzyme CYP3A4.

ABSTRACT: We report the synthesis and photochemical and biological characterization of the first selective and potent metal-based inhibitors of cytochrome P450 3A4 (CYP3A4), the major human drug metabolizing enzyme. Five Ru(II)-based derivatives were prepared from two analogs of the CYP3A4 inhibitor ritonavir, 4 and 6: [Ru(tpy)(L)(6)]Cl₂ (tpy = 2,2':6',2″-terpyridine) with L = 6,6'-dimethyl-2,2'-bipyridine (Me₂bpy; 8), dimethylbenzo[i]dipyrido[3,2-a:2',3'-c]phenazine (Me₂dppn; 10) and 3,6-dimethyl-10,15-diphenylbenzo[i]dipyrido[3,2-a:2',3'-c]phenazine (Me₂Ph₂dppn; 11), [Ru(tpy)(Me₂bpy)(4)]Cl₂ (7) and [Ru(tpy)(Me₂dppn

SUBMITTER: Toupin N 

PROVIDER: S-EPMC8265689 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature