Issue 11, 2015

Design, synthesis and bioevaluation of tacrine hybrids with cinnamate and cinnamylidene acetate derivatives as potential anti-Alzheimer drugs

Abstract

A series of novel tacrine–cinnamate and tacrine–cinnamylidene acetate hybrids have been designed, synthesized and evaluated as multitarget compounds for the treatment of Alzheimer's disease. Results of the assessment of their inhibitory activity against acetylcholinesterase (AChE), antioxidant activity and self-induced β-amyloid (Aβ) aggregation are reported. These hybrid compounds showed promising results: all presented high activity against AChE, with IC50 values between the low micromolar and nanomolar range of concentrations. The molecular modeling studies suggested dual interaction with both the catalytic and peripheral sites. Some compounds presented good antioxidant activity (DPPH free radical method) in the low micromolar range, namely the cinnamate derivatives with hydroxyl substituents and extended allyl-conjugation. Moreover, these compounds showed good neuroprotective effects by rescuing neuroblastoma cells stressed with the β-amyloid peptide and hydrogen peroxide. Overall, our results suggest that some of these new hybrids have good potential as multifunctional drug candidates for AD treatment.

Graphical abstract: Design, synthesis and bioevaluation of tacrine hybrids with cinnamate and cinnamylidene acetate derivatives as potential anti-Alzheimer drugs

Supplementary files

Article information

Article type
Concise Article
Submitted
04 Jun 2015
Accepted
31 Aug 2015
First published
02 Sep 2015

Med. Chem. Commun., 2015,6, 1969-1977

Design, synthesis and bioevaluation of tacrine hybrids with cinnamate and cinnamylidene acetate derivatives as potential anti-Alzheimer drugs

C. Quintanova, R. S. Keri, S. M. Marques, M. G-Fernandes, S. M. Cardoso, M. Luísa Serralheiro and M. Amélia Santos, Med. Chem. Commun., 2015, 6, 1969 DOI: 10.1039/C5MD00236B

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.

Spotlight

Advertisements