Design, synthesis and in vitro evaluation of indolotacrine analogues as multitarget-directed ligands for the treatment of Alzheimer's disease

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F16%3A43915050" target="_blank" >RIV/00023752:_____/16:43915050 - isvavai.cz</a>
Alternative codes found
RIV/60162694:G44__/16:43875619 RIV/62690094:18470/16:50004736 RIV/00216208:11160/16:10324912 RIV/00179906:_____/16:10324912
Result on the web
<a href="http://onlinelibrary.wiley.com/doi/10.1002/cmdc.201500383/abstract" target="_blank" >http://onlinelibrary.wiley.com/doi/10.1002/cmdc.201500383/abstract</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/cmdc.201500383" target="_blank" >10.1002/cmdc.201500383</a>

Result language
angličtina
Original language name
Design, synthesis and in vitro evaluation of indolotacrine analogues as multitarget-directed ligands for the treatment of Alzheimer's disease
Original language description
Novel indolotacrine analogues were designed, synthesized, and evaluated as potential drugs for the treatment of Alzheimer's disease. By using a multitarget-directed ligand approach, compounds were designed to act simultaneously as cholinesterase (ChE) and monoamine oxidase (MAO) inhibitors. The compounds were also evaluated for antioxidant, cytotoxic, hepatotoxic, and blood-brain barrier (BBB) permeability properties. Indolotacrine 9b (9-methoxy-2,3,4,6-tetrahydro-1H-indolo[2,3-b]quinolin-11-amine) showed the most promising results in the in vitro assessment; it is a potent inhibitor of acetylcholinesterase (AChE IC50: 1.5 mu m), butyrylcholinesterase (BChE IC50: 2.4 mu m) and MAO A (IC50: 0.49 mu m), and it is also a weak inhibitor of MAO B (IC50: 53.9 mu m). Although its cytotoxic (IC50: 5.5 +/- 0.4 mu m) and hepatotoxic (IC50: 1.22 +/- 0.11 mu m) profiles are not as good as those of the standard 7-methoxytacrine (IC50: 63 +/- 4 and 11.50 +/- 0.77 mu m, respectively), the overall improvement in the inhibitory activities and potential to cross the BBB make indolotacrine 9b a promising lead compound for further development and investigation.
Czech name
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Czech description
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Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
FH - Neurology, neuro-surgery, nuero-sciences
OECD FORD branch
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Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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