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Publication Abstract from PubMed

Liver fructose-1,6-bisphosphatase (FBPase) is a key enzyme in the gluconeogenesis, and its inhibitors are expected to be novel antidiabetic agents. Herein, a series of new indole and benzofuran analogues were designed and synthesized to evaluate the inhibitory activity against FBPase. As a result, the novel FBPase inhibitors bearing N-acylsulfonamide moiety on the 3-position of the indole-2-carboxylic acid scaffold (compounds 22f and 22g) were identified with IC(50)s at the submicromolar levels. Three X-ray crystal structures of the complexes were solved and revealed the structural basis for the inhibitory activity. The chemoinformatics analysis further disclosed the distinct binding features of this class of inhibitors, providing an insight for further modifications to create structurally distinct FBPase inhibitors with high potency and drug-like properties.

Discovery of Novel Indole Derivatives as Fructose-1,6-bisphosphatase Inhibitors and X-ray Cocrystal Structures Analysis.,Wang X, Zhao R, Ji W, Zhou J, Liu Q, Zhao L, Shen Z, Liu S, Xu B ACS Med Chem Lett. 2021 Dec 20;13(1):118-127. doi: , 10.1021/acsmedchemlett.1c00613. eCollection 2022 Jan 13. PMID:35059131^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.