Synthesis and evaluation of oxindoles as promising inhibitors of the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1.

ABSTRACT: Indoleamine 2,3-dioxygenase 1 (IDO1) is considered as an important therapeutic target for the treatment of cancer, chronic infections and other diseases that are associated with immune suppression. Recent developments in understanding the catalytic mechanism of the IDO1 enzyme revealed that conversion of l-tryptophan (l-Trp) to N-formylkynurenine proceeded through an epoxide intermediate state. Accordingly, we synthesized a series of 3-substituted oxindoles from l-Trp, tryptamine and isatin. Compounds with C3-substituted oxindole moieties showed moderate inhibitory activity against the purified human IDO1 enzyme. Their optimization led to the identification of potent compounds, 6, 22, 23 and 25 (IC₅₀ = 0.19 to 0.62 μM), which are competitive in

SUBMITTER: Paul S 

PROVIDER: S-EPMC6071943 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature