Steroidal alkaloids from Holarrhena antidysenterica as acetylcholinesterase inhibitors and the investigation for structure-activity relationships

Life Sciences
Zhong-Duo YangShuo Li

Abstract

Inhibition of acetylcholinesterase (AChE) is still considered as a strategy for the treatment of neurological disorders such as Alzheimer's disease (AD). Many plant derived alkaloids (such as huperzine A, galanthamine and rivastigmine) are known for their AChE inhibitory activity. The aim of the present work was to isolate and identify new AChE inhibitors from Holarrhen antidysenterica. These compounds were tested for AChE inhibiting activity by the Ellman's method in 96-well microplates. In addition, molecular modeling was performed to explore the binding mode of inhibitors 1-5 at the active site of AChE, and the preliminary structure-activity relationships (SARs) were discussed. In the course of searching for AChE inhibitors from herb medicines, the total alkaloidal extract from the seeds of H. antidysenterica was found having potent AChE inhibitory activity with an IC(50) value of 6.1 μg/mL. Further bioactivity-guided chromatographic fractionation afforded five steroidal alkaloids, conessine 1, isoconessimine 2, conessimin 3, conarrhimin 4 and conimin 5. All the isolated compounds, except for 2, showed strong AChE inhibiting activity with IC(50) values ranging from 4 to 28 μM. The most active inhibitor is compound 3 with an ...Continue Reading

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Citations

Nov 19, 2013·The Journal of Pharmacy and Pharmacology·Eduardo Luis KonrathAmélia T Henriques
Jul 8, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Charles Okeke NnadiThomas J Schmidt
Nov 28, 2017·Natural Product Research·Sarot CheenprachaStephen G Pyne
Dec 24, 2015·Organic & Biomolecular Chemistry·Elisabeth K OlsenJeanette H Andersen
Nov 14, 2012·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Grasiely F SousaJacqueline A Takahashi
Dec 8, 2015·Clinical Chemistry and Laboratory Medicine : CCLM·Serena RicciAngelina Di Carlo
Feb 20, 2020·Current Medicinal Chemistry·Natália Martins, Isabel C F R Ferreira
Aug 6, 2021·Natural Product Research·Li-Jun YangZong-Mei Shu

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