Bivalent ligands incorporating curcumin and diosgenin as multifunctional compounds against Alzheimer’s disease
[Display omitted] In an effort to combat the multifaceted nature of Alzheimer’s disease (AD) progression, a series of multifunctional, bivalent compounds containing curcumin and diosgenin were designed, synthesized, and biologically characterized. Screening results in MC65 neuroblastoma cells establ...
Saved in:
Published in | Bioorganic & medicinal chemistry Vol. 23; no. 22; pp. 7324 - 7331 |
---|---|
Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
OXFORD
Elsevier Ltd
15.11.2015
Elsevier |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | [Display omitted]
In an effort to combat the multifaceted nature of Alzheimer’s disease (AD) progression, a series of multifunctional, bivalent compounds containing curcumin and diosgenin were designed, synthesized, and biologically characterized. Screening results in MC65 neuroblastoma cells established that compound 38 with a spacer length of 17 atoms exhibited the highest protective potency with an EC50 of 111.7±9.0nM. A reduction in protective activity was observed as spacer length was increased up to 28 atoms and there is a clear structural preference for attachment to the methylene carbon between the two carbonyl moieties of curcumin. Further study suggested that antioxidative ability and inhibitory effects on amyloid-β oligomer (AβO) formation may contribute to the neuroprotective outcomes. Additionally, compound 38 was found to bind directly to Aβ, similar to curcumin, but did not form complexes with the common biometals Cu, Fe, and Zn. Altogether, these results give strong evidence to support the bivalent design strategy in developing novel compounds with multifunctional ability for the treatment of AD. |
---|---|
Bibliography: | NIH RePORTER ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0968-0896 1464-3391 |
DOI: | 10.1016/j.bmc.2015.10.032 |