Designing inhibitors against fructose 1,6-bisphosphatase: exploring natural products for novel inhibitor scaffolds.

European Journal of Medicinal Chemistry
Sabrina HengEvan R Kantrowitz

Abstract

Natural products often contain unusual scaffold structures that may be elaborated by combinatorial methods to develop new drug-like molecules. Visual inspection of more than 128 natural products with some type of anti-diabetic activity suggested that a subset might provide novel scaffolds for designing potent inhibitors against fructose 1,6-bisphosphatase (FBPase), an enzyme critical in the control of gluconeogenesis. Using in silico docking methodology, these were evaluated to determine those that exhibited affinity for the AMP binding site. Achyrofuran from the South American plant Achyrocline satureoides, was selected for further investigation. Using the achyrofuran scaffold, inhibitors against FBPase were developed. Compounds 15 and 16 inhibited human liver and pig kidney FBPases at IC50 values comparable to that of AMP, the natural allosteric inhibitor.

Citations

Apr 7, 2016·Scientifica·Swati ChaturvediSudipta Saha
Jan 15, 2015·European Journal of Medicinal Chemistry·Brian E Love
May 4, 2016·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·Xinya HanJian Wan
Dec 3, 2014·European Journal of Medicinal Chemistry·Jianbo BieZhufang Shen
Dec 18, 2014·Journal of Natural Products·Carina CaseroAna Estévez-Braun
Sep 8, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jirawat RiyaphanChing-Feng Weng
May 5, 2020·Journal of Natural Products·Carina ProençaEduarda Fernandes

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