Discovery of novel indole derivatives as allosteric inhibitors of fructose-1,6-bisphosphatase

•Novel indole derivatives were synthesized as FBPase inhibitors.•Compound 14c exhibited potent inhibitory activity.•Structure-activity relationships were explored together with Docking study.

A series of novel indole derivatives was designed and synthesized as inhibitors of fructose-1,6-bisphosphatase (FBPase). The most potent compound 14c was identified with an IC50 value of 0.10 μM by testing the inhibitory activity against recombinant human FBPase. The structure-activity relationships were investigated on the substitution at 4- and 5-position of the indole scaffold. The binding interactions of the title compounds at AMP binding site of FBPase were predicted using CDOCKER algorithm.

Graphical abstractA series of novel 3-(2-carboxyethyl)-7-nitro-1H-indole-2-carboxylic acid derivatives were synthesized and evaluated as fructose-1,6-bisphosphatase inhibitors. R4, R5 = hydrogen, halogen, alkyl, aryl and arylamino groups.Figure optionsDownload full-size imageDownload as PowerPoint slide