Synthesis and evaluation of frentizole-based indolyl thiourea analogues as MAO/ABAD inhibitors for Alzheimer's disease treatment

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F17%3A50005605" target="_blank" >RIV/62690094:18470/17:50005605 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11160/17:10359065 RIV/00179906:_____/17:10359065

Result on the web

<a href="http://www.sciencedirect.com/science/article/pii/S0968089616314523" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0968089616314523</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bmc.2016.12.029" target="_blank" >10.1016/j.bmc.2016.12.029</a>

Result language

angličtina

Original language name

Synthesis and evaluation of frentizole-based indolyl thiourea analogues as MAO/ABAD inhibitors for Alzheimer's disease treatment

Original language description

Alzheimer&apos;s disease (AD) is a neurodegenerative disorder associated with an excessive accumulation of amyloid-beta peptide (A beta). Based on the multifactorial nature of AD, preparation of multi-target-directed ligands presents a viable option to address more pathological events at one time. A novel class of asymmetrical disubstituted indolyl thioureas have been designed and synthesized to interact with monoamine oxidase (MAO) and/or amyloid-binding alcohol dehydrogenase (ABAD). The design combines the features of known MAO inhibitors scaffolds (e.g. rasagiline or ladostigil) and a frentizole moiety with potential to interact with ABAD. Evaluation against MAO identified several compounds that inhibited in the low to moderate micromolar range. The most promising compound (19) inhibited human MAO-A and MAO-B with IC50 values of 6.34 mu M and 030 mu M, respectively. ABAD activity evaluation did not show any highly potent compound, but the compound series allowed identification of structural features to assist the future development of ABAD inhibitors. Finally, several of the compounds were found to be potent inhibitors of horseradish peroxidase (HRP), preventing the use of the Amplex (TM) Red assay to detect hydrogen peroxide produced by MAO, highlighting the need for serious precautions when using an enzyme-coupled assay.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30104 - Pharmacology and pharmacy

Project

<a href="/en/project/NV15-28967A" target="_blank" >NV15-28967A: Modulators of mitochondrial enzymes for treatment of neurodegenerative disorders</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Bioorganic and medicinal chemistry

ISSN

0968-0896

e-ISSN

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Volume of the periodical

25

Issue of the periodical within the volume

3

Country of publishing house

GB - UNITED KINGDOM

Number of pages

10

Pages from-to

1143-1152

UT code for WoS article

000394201900031

EID of the result in the Scopus database

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