Ethylnaphthoquinone derivatives as inhibitors of indoleamine-2, 3-dioxygenase from the mangrove endophytic fungus Neofusicoccum austral SYSU-SKS024

Abstract

Bioassay-guided fractionation of the dichloromethane extract of the fungus Neofusicoccum austral SYSU-SKS024 led to the isolation of three new ethylnaphthoquinone derivatives, neofusnaphthoquinone A (1), 6-(1-methoxylethy1)-2,7-dimethoxyjuglone (2), (3R,4R)-3-methoxyl-botryosphaerone D (6), together with six known analogs (3-5 and 7-9). Their structures were elucidated by spectroscopic analysis and single crystal X-ray diffraction analysis. Neofusnaphthoquinone A (1) is the third example of the unsymmetrical naphthoquinone dimer, which is rarely found in natural source. All of the isolates were evaluated for their indoleamine 2, 3-dioxygenase (IDO) inhibitory activity, compounds 1-6 showed in vitro inhibitory effects against IDO with IC₅₀ values ranging from 0.11 to 10.92μM. This is the first time naphthoquinone dimer (1), as a novel carbon skeleton possessing IDO inhibitory activity, was reported.

Keywords: Ethylnaphthoquinone; Indoleamine-2, 3-dioxygenase; Neofusicoccum.