Abstract
BACE-1, an aspartyl protease is implicated in Alzheimer’s disease. In this paper, we report BACE-1 inhibitory potential of acridin-9-yl hydrazide derivatives, known to inhibit other aspartyl proteases. The derivatives were designed based on the docking study, synthesized and assessed for BACE-1 inhibition in vitro. Docking simulation predicted the binding of prototype acridin-9-yl hydrazide at BACE-1 active site. The enzyme–inhibitor complex was primarily stabilized by hydrogen bonds between the hydrazide part of the inhibitor and side chain of Gly11, which is important amino acid of 10s loop. The acridinyl moiety showed π–π stacking with Tyr71 while the phenyl ring was buried in S1 cavity. Enzyme inhibition experiments showed that the synthesized compounds had moderate activity with compound AA-13 having 54.54 % inhibition at 10 µM concentration.
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Jain, P., Wadhwa, P.K. & Jadhav, H.R. Design, synthesis and evaluation of acridin-9-yl hydrazide derivatives as BACE-1 inhibitors. Med Chem Res 25, 1507–1513 (2016). https://doi.org/10.1007/s00044-016-1581-3
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DOI: https://doi.org/10.1007/s00044-016-1581-3