Novel steroid inhibitors of glucose 6-phosphate dehydrogenase.

@article{Hamilton2012NovelSI,
  title={Novel steroid inhibitors of glucose 6-phosphate dehydrogenase.},
  author={Niall Morton Hamilton and Martin Dawson and Emma E. Fairweather and Nicola S Hamilton and James R. Hitchin and Dominic I. James and Stuart Donald Jones and Allan M. Jordan and Amanda J. Lyons and Helen F. Small and Graeme J. Thomson and Ian D. Waddell and Donald J. Ogilvie},
  journal={Journal of medicinal chemistry},
  year={2012},
  volume={55 9},
  pages={
          4431-45
        }
}
Novel derivatives of the steroid DHEA 1, a known uncompetitive inhibitor of G6PD, were designed, synthesized, and tested for their ability to inhibit this dehydrogenase enzyme. Several compounds with approximately 10-fold improved potency in an enzyme assay were identified, and this improved activity translated to efficacy in a cellular assay. The SAR for steroid inhibition of G6PD has been substantially developed; the 3β-alcohol can be replaced with 3β-H-bond donors such as sulfamide… Expand
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Abstract New synthetic DHEA conjugates were tested for their capacity as inhibitors of purified human placental G-6-PDH. Although most of these derivatives like DHEA alkyl sulfates, alkyl sulfonatesExpand
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TLDR
Results demonstrate that steroids inhibit glucose 6-phosphate dehydrogenase by binding to the ternary enzyme-coenzyme-substrate ternARY complex(es), the first direct demonstration that uncompetitive inhibition of a two- Substrate enzyme, by compounds other than its substrates or products, can occur by binding of the inhibitor to a ternaries complex. Expand
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TLDR
The esterification with sulfatidic acid markedly enhances the inhibition of this enzyme and the interaction between steroids or steroid conjugates and G-6-PDH, eventually leading to an allosteric inhibition of the enzyme. Expand
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Abstract Various synthetic C19- and C20-steroids or their derivatives, including a series of new compounds, were tested as inhibitors of human placental glucose-6-phosphate dehydrogenase. The alkylExpand
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Various 3β-substituted Δ5-(Δ4) C19- or C21-steroids were tested as inhibitors of human red blood cell glucose-6-phosphate dehydrogenase. From the results obtained it was concluded that the presenceExpand
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Calculations using the PM3 semi-empirical method upon 22 steroids related to androstane are used in an analysis of their activity as inhibitors of glucose-6-phosphate dehydrogenase. Structures andExpand
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TLDR
It is shown that endogenous DHEA metabolites also have an anti-proliferative action that is not induced by inhibiting G6PD or HMGR activity alone, and these non-androgenic D HEA metabolites may serve as chemopreventive or anti-Proliferatives therapies. Expand
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Abstract By incubation of purified human placental glucose-6-phosphate dehydrogenase with C18steroids it could be demonstrated that only 17-oxo compounds such as estrone, 2-methoxyestrone,Expand
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