Plant isoquinoline alkaloids as potential neurodrugs: A comparative study of the effects of benzo[c]phenanthridine and berberine-based compounds on ß-amyloid aggregation.
Chem Biol Interact
; 334: 109300, 2021 Jan 25.
Article
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| MEDLINE
| ID: mdl-33098838
ABSTRACT
Herein we present a comparative study of the effects of isoquinoline alkaloids belonging to benzo[c]phenanthridine and berberine families on ß-amyloid aggregation. Results obtained using a Thioflavine T (ThT) fluorescence assay and circular dichroism (CD) spectroscopy suggested that the benzo[c]phenanthridine nucleus, present in both sanguinarine and chelerythrine molecules, was directly involved in an inhibitory effect of Aß1-42 aggregation. Conversely, coralyne, that contains the isomeric berberine nucleus, significantly increased propensity for Aß1-42 to aggregate. Surface Plasmon Resonance (SPR) experiments provided quantitative estimation of these interactions coralyne bound to Aß1-42 with an affinity (KDâ¯=â¯11.6⯵M) higher than benzo[c]phenanthridines. Molecular docking studies confirmed that all three compounds are able to recognize Aß1-42 in different aggregation forms suggesting their effective capacity to modulate the Aß1-42 self-recognition mechanism. Molecular dynamics simulations indicated that coralyne increased the ß-content of Aß1-42, in early stages of aggregation, consistent with fluorescence-based promotion of the Aß1-42 self-recognition mechanism by this alkaloid. At the same time, sanguinarine induced Aß1-42 helical conformation corroborating its ability to delay aggregation as experimentally proved in vitro. The investigated compounds were shown to interfere with aggregation of Aß1-42 demonstrating their potential as starting leads for the development of therapeutic strategies in neurodegenerative diseases.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Fenantridinas
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Plantas
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Berberina
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Péptidos beta-Amiloides
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Fármacos Neuroprotectores
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Alcaloides
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Agregado de Proteínas
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Isoquinolinas
Límite:
Humans
Idioma:
En
Año:
2021
Tipo del documento:
Article