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Steroidal alkaloids from Holarrhena antidysenterica as acetylcholinesterase inhibitors and the investigation for structure-activity relationships
Steroidal alkaloids from Holarrhena antidysenterica as acetylcholinesterase inhibitors and the investigation for structure-activity relationships
- Source :
- Life sciences. 90(23-24)
- Publication Year :
- 2011
-
Abstract
- Aims 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 . Main methods 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. Key findings 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 IC 50 value of 4 μM. The mode of AChE inhibition by 3 was reversible and non-competitive. Significance The results suggest that these alkaloids could be potential candidates for further development of new drugs against AD.
- Subjects :
- Models, Molecular
medicine.drug_class
Aché
Pharmacology
General Biochemistry, Genetics and Molecular Biology
chemistry.chemical_compound
Inhibitory Concentration 50
Structure-Activity Relationship
Alkaloids
medicine
Structure–activity relationship
General Pharmacology, Toxicology and Pharmaceutics
Huperzine A
Holarrhena
Rivastigmine
biology
Chemistry
Plant Extracts
General Medicine
biology.organism_classification
Acetylcholinesterase
language.human_language
Conessine
Acetylcholinesterase inhibitor
Seeds
language
Steroids
Cholinesterase Inhibitors
medicine.drug
Subjects
Details
- ISSN :
- 18790631
- Volume :
- 90
- Issue :
- 23-24
- Database :
- OpenAIRE
- Journal :
- Life sciences
- Accession number :
- edsair.doi.dedup.....42eb204a6a9d0fdc13f9535a0fc6814b