L-Dopa and dopamine conjugated naphthalenediimides modulate amyloid beta toxicity

Ramesh, Madhu and Makam, Pandeeswar and Voshavar, Chandrashekhar and Khare, Harshavardhan and Rajasekhar, Kolla and Ramakumar, Suryanarayanarao and Govindaraju, Thimmaiah (2018) L-Dopa and dopamine conjugated naphthalenediimides modulate amyloid beta toxicity. In: ORGANIC & BIOMOLECULAR CHEMISTRY, 16 (41). pp. 7682-7692.

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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 (A) 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 A 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 A aggregation, NLD and NDP possess antioxidant activity conducive to the development of disease-modifying therapeutic agents for the treatment of Alzheimer's disease.

Item Type:	Journal Article
Publication:	ORGANIC & BIOMOLECULAR CHEMISTRY
Publisher:	ROYAL SOC CHEMISTRY
Additional Information:	Copy right for this article belong to ROYAL SOC CHEMISTRY
Department/Centre:	Division of Physical & Mathematical Sciences > Physics
Date Deposited:	12 Nov 2018 15:43
Last Modified:	25 Aug 2022 05:33
URI:	https://eprints.iisc.ac.in/id/eprint/61018

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