Design of novel monoamine oxidase-B inhibitors based on piperine scaffold: Structure-activity-toxicity, drug-likeness and efflux transport studies.
Alkaloids
/ chemical synthesis
Benzodioxoles
/ chemical synthesis
Caco-2 Cells
Cell Differentiation
/ drug effects
Cell Survival
/ drug effects
Dose-Response Relationship, Drug
Drug Design
Humans
Ligands
Molecular Structure
Monoamine Oxidase
/ metabolism
Monoamine Oxidase Inhibitors
/ chemical synthesis
Neuroprotective Agents
/ chemical synthesis
Oxidative Stress
/ drug effects
Piperidines
/ chemical synthesis
Polyunsaturated Alkamides
/ chemical synthesis
Structure-Activity Relationship
Tumor Cells, Cultured
Monoamine oxidase
P-gp
Parkinson's disease
Piperine
Structure-activity-toxicity relationship
Journal
European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510
Informations de publication
Date de publication:
01 Jan 2020
01 Jan 2020
Historique:
received:
18
08
2019
revised:
06
10
2019
accepted:
06
10
2019
pubmed:
13
11
2019
medline:
19
2
2020
entrez:
13
11
2019
Statut:
ppublish
Résumé
Piperine has been associated with neuroprotective effects and monoamine oxidase (MAO) inhibition, thus being an attractive scaffold to develop new antiparkinsonian agents. Accordingly, we prepared a small library of piperine derivatives and screened the inhibitory activities towards human MAO isoforms (hMAO-A and hMAO-B). Structure-activity relationship (SAR) studies pointed out that the combination of α-cyano and benzyl ester groups increased both potency and selectivity towards hMAO-B. Kinetic experiments with compounds 7, 10 and 15 indicated a competitive hMAO-B inhibition mechanism. Compounds 15 and 16, at 10 μM, caused a small but significant decrease in P-gp efflux activity in Caco-2 cells. Compound 15 stands out as the most potent piperine-based hMAO-B inhibitor (IC
Identifiants
pubmed: 31711793
pii: S0223-5234(19)30922-5
doi: 10.1016/j.ejmech.2019.111770
pii:
doi:
Substances chimiques
Alkaloids
0
Benzodioxoles
0
Ligands
0
Monoamine Oxidase Inhibitors
0
Neuroprotective Agents
0
Piperidines
0
Polyunsaturated Alkamides
0
Monoamine Oxidase
EC 1.4.3.4
piperine
U71XL721QK
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
111770Informations de copyright
Copyright © 2019 Elsevier Masson SAS. All rights reserved.