(A) The chemical structure of mumbaistatin. Mumbaistatin is an extremely potent inhibitor of glucose-6-phosphate translocase (IC50 = 5 nM). The core of the molecule is a reduced carboxylic acid containing anthraquinone, which is also observed in compounds such as DMAC, YT127, and YT127b.
(B) Inhibition of glucose-6-phosphate translocase activity by novel anthraquinones. The inhibition assay is performed as described in the experimental section. The control contains the rat liver microsome and glucose-6-phosphate only. Chlorogenic acid (IC50 = 0.26 mM) was used as a reference. The G6Pase activity of the microsome in the presence of six anthraquinones (DMAC, 3, 4, 7, 8, and 9) was measured. For each compound, three different concentrations (50, 25, and 12.5 mM) were used to detect dose-dependent inhibition. No inhibition was observed for DMAC or 7. Dose-dependent inhibition was observed for compounds 3,
4, 8, and 9.