Issue 48, 2020, Issue in Progress

Aryldiazoquinoline based multifunctional small molecules for modulating Aβ42 aggregation and cholinesterase activity related to Alzheimer's disease

Abstract

Research continues to find a breakthrough for the treatment of Alzheimer's Disease (AD) due to its complicated pathology. Presented herein is a novel series of arydiazoquinoline molecules investigated for their multifunctional properties against the factors contributing to Alzheimer's disease (AD). The inhibitory properties of fourteen closely related aryldiazoquinoline derivatives have been evaluated for their inhibitory effect on Aβ42 peptide aggregation. Most of these molecules inhibited Aβ42 fibrillation by 50–80%. Selected molecules were also investigated for their binding behaviour to preformed Aβ40 aggregates indicating a nanomolar affinity. In addition, these compounds were further investigated as cholinesterase inhibitors. Interestingly, some of the compounds turned out to be moderate in vitro inhibitors for AChE activity with IC50 values in low micro molar range. The highest anti-AChE activity was shown by compound labelled as 2a with an IC50 value of 6.2 μM followed by 2b with IC50 value of 7.0 μM. In order to understand the inhibitory effect, binding of selected molecules to AChE enzyme was studied using molecular docking. In addition, cell toxicity studies using Neuro2a cells were performed to assess their effect on neuronal cell viability which suggests that these molecules possess a non-toxic molecular framework. Overall, the study identifies a family of molecules that show good in vitro anti-Aβ-aggregation properties and moderately inhibit cholinesterase activity.

Graphical abstract: Aryldiazoquinoline based multifunctional small molecules for modulating Aβ42 aggregation and cholinesterase activity related to Alzheimer's disease

Supplementary files

Article information

Article type
Paper
Submitted
12 Jun 2020
Accepted
22 Jul 2020
First published
04 Aug 2020
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2020,10, 28827-28837

Aryldiazoquinoline based multifunctional small molecules for modulating Aβ42 aggregation and cholinesterase activity related to Alzheimer's disease

M. Rana, A. Pareek, S. Bhardwaj, G. Arya, S. Nimesh, H. Arya, T. K. Bhatt, S. Yaragorla and A. K. Sharma, RSC Adv., 2020, 10, 28827 DOI: 10.1039/D0RA05172A

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, 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 commercial 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