Discovery of Novel Indoleamine 2,3-Dioxygenase 1 (IDO1) and Histone Deacetylase 1 (HDAC1) Dual Inhibitors Derived from the Natural Product Saprorthoquinone.

ABSTRACT: The discovery of IDO1 and HDAC1 dual inhibitors may provide a novel strategy for cancer treatment by taking advantages of both immunotherapeutic and epigenetic drugs. In this paper, saprorthoquinone (1) and 13 of its analogues from Salvia prionitis Hance were investigated for their SAR against IDO1, the results demonstrated the ortho-quinone was a key pharmacophore. Then a series of IDO1 and HDAC dual inhibitors connected by appropriate linkers were designed, synthesized, and evaluated from the hit compound saprorthoquinone (1). Among them, compound 33d showed balanced activity against both IDO1 (IC₅₀ = 0.73 μM) and HDAC1 (IC₅₀ = 0.46 μM). Importantly, the structure of 33d suggested that an ortho-quinone pharmacophore a

SUBMITTER: Lin Y 

PROVIDER: S-EPMC7582476 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature