Issue 41, 2018

l-Dopa and dopamine conjugated naphthalenediimides modulate amyloid β toxicity

Abstract

The process of protein misfolding and aggregation to form neurotoxic species is strongly implicated in most of the neurodegenerative disorders. In particular, amyloid beta (Aβ) misfolding and aggregation is central to pathophysiological processes of Alzheimer's disease. The development of aggregation modulators has enormous implications in the discovery of effective therapeutic agents for Alzheimer's disease. Herein, we report the design and synthesis of a series of natural amino acid, L-dopa and dopamine appended derivatives of naphthalenediimide (NDI) to identify efficient aggregation modulators. Furthermore, the molecular docking studies revealed the possible binding sites and binding mode of NDI-conjugates to Aβ aggregates. Among the designed NDI-conjugates, L-dopa and dopamine derivatives (NLD and NDP, respectively) showed excellent aggregation modulation efficiency (inhibition and dissolution), as shown by the thioflavin T (ThT) binding assays, dot blot analysis and in cellulo studies. The docking results from in silico studies are in good agreement with the experimental data. In addition to their significant modulation efficiency towards Aβ aggregation, NLD and NDP possess antioxidant activity conducive to the development of disease-modifying therapeutic agents for the treatment of Alzheimer's disease.

Graphical abstract: l-Dopa and dopamine conjugated naphthalenediimides modulate amyloid β toxicity

Supplementary files

Article information

Article type
Paper
Submitted
16 юли 2018
Accepted
26 сеп 2018
First published
28 сеп 2018

Org. Biomol. Chem., 2018,16, 7682-7692

L-Dopa and dopamine conjugated naphthalenediimides modulate amyloid β toxicity

M. Ramesh, P. Makam, C. Voshavar, H. Khare, K. Rajasekhar, S. Ramakumar and T. Govindaraju, Org. Biomol. Chem., 2018, 16, 7682 DOI: 10.1039/C8OB01691G

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements