Plant isoquinoline alkaloids as potential neurodrugs: A comparative study of the effects of benzo[c]phenanthridine and berberine based compounds on β-amyloid aggregation
Plant isoquinoline alkaloids as potential neurodrugs: A comparative study of the effects of benzo[c]phenanthridine and berberine based compounds on β-amyloid aggregation(558 views) Marasco D, Vicidomini C, Krupa P, Cioffi F, Pham DQH, Li MS, Florio D, Broersen K, De Pandis MF, Roviello GN
Chem Biol Interact (ISSN: 0009-2797linking), 2021 Jan 25; 334: 109300-109301.
Department of Pharmacy, University of Naples Federico II, Via Mezzocannone 16, 80134, Naples, Italy
Istituto di Biostrutture e Bioimmagini IBB - CNR, Via Mezzocannone 16, I-80134 Naples, Italy.
Institute of Physics Polish Academy of Sciences, Al. Lotników 32/46, 02-668, Warsaw, Poland.
Nanobiophysics Group, Technical Medical Centre, Faculty of Science and Technology, University of Twente, Enschede, the Netherlands.
Institute for Computational Sciences and Technology, SBI building, Quang Trung Software City, Tan ChanhHiep Ward, District 12, Ho Chi Minh City, Viet Nam.
Applied Stem Cell Technologies, Technical Medical Centre, Faculty of Science and Technology, University of Twente, Enschede, the Netherlands.
San Raffaele Cassino Institute, San Raffaele SPA, 03043, Cassino, FR, Italy.
References: Not available.
Plant isoquinoline alkaloids as potential neurodrugs: A comparative study of the effects of benzo[c]phenanthridine and berberine based compounds on β-amyloid aggregation
Herein we present a comparative study of the effects of isoquinoline alkaloids belonging to benzo[c]phenanthridine and berberine families on β-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 Aβ(1-42) aggregation. Conversely, coralyne, that contains the isomeric berberine nucleus, significantly increased propensity for Aβ(1-42) to aggregate. Surface Plasmon Resonance (SPR) experiments provided quantitative estimation of these interactions: coralyne bound to Aβ(1-42) with an affinity (K(D) = 11.6 μM) higher than benzo[c]phenanthridines. Molecular docking studies confirmed that all three compounds are able to recognize Aβ(1-42) in different aggregation forms suggesting their effective capacity to modulate the Aβ(1-42) self-recognition mechanism. Molecular dynamics simulations indicated that coralyne increased the β-content of Aβ(1-42), in early stages of aggregation, consistent with fluorescence-based promotion of the Aβ(1-42) self-recognition mechanism by this alkaloid. At the same time, sanguinarine induced Aβ(1-42) helical conformation corroborating its ability to delay aggregation as experimentally proved in vitro. The investigated compounds were shown to interfere with aggregation of Aβ(1-42) demonstrating their potential as starting leads for the development of therapeutic strategies in neurodegenerative diseases.
Plant isoquinoline alkaloids as potential neurodrugs: A comparative study of the effects of benzo[c]phenanthridine and berberine based compounds on β-amyloid aggregation
Plant isoquinoline alkaloids as potential neurodrugs: A comparative study of the effects of benzo[c]phenanthridine and berberine based compounds on β-amyloid aggregation