Issue 36, 2022

Synthesis of novel benzothiazole derivatives and investigation of their enzyme inhibitory effects against Alzheimer's disease

Abstract

The use of dual acetylcholinesterase (AChE)–monoamine oxidase B (MAO-B) inhibitors is a new approach in the treatment of Alzheimer disease (AD). In this work, 14 new benzothiazoles (4a–4n) were designed and synthesized. In biological activity studies, the AChE, butyrylcholinesterase (BChE), MAO-A and MAO-B inhibitory potentials of all compounds were evaluated using the in vitro fluorometric method. Additionally, amyloid beta (Aβ)-aggregation inhibitory effects of active compounds were evaluated by means of an in vitro kit-based method. The biological evaluation showed that compounds 4a, 4d, 4f, 4h, 4k and 4m displayed significant activity against AChE and MAO-B enzymes. Compound 4f displayed inhibitory activity against AChE and MAO-B enzyme with IC50 values of 23.4 ± 1.1 nM and 40.3 ± 1.7 nM, respectively. It has been revealed that compound 4f may have the potential to inhibit AChE and MAO-B enzymes, as well as the ability to prevent the formation of beta amyloid plaques accumulated in the brains of patients suffering from AD. In silico studies also support the obtained biological activity findings. Compound 4f provided strong interactions with the active site of both enzymes. In particular, the interaction of compound 4f with flavin adenine dinucleotide (FAD) in the MAO-B enzyme active site is a promising and exciting finding.

Graphical abstract: Synthesis of novel benzothiazole derivatives and investigation of their enzyme inhibitory effects against Alzheimer's disease

Supplementary files

Article information

Article type
Paper
Submitted
20 jún. 2022
Accepted
22 júl. 2022
First published
19 ágú. 2022
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2022,12, 23626-23636

Synthesis of novel benzothiazole derivatives and investigation of their enzyme inhibitory effects against Alzheimer's disease

Ş. Karaca, D. Osmaniye, B. N. Sağlık, S. Levent, S. Ilgın, Y. Özkay, A. Ç. Karaburun, Z. A. Kaplancıklı and N. Gundogdu-Karaburun, RSC Adv., 2022, 12, 23626 DOI: 10.1039/D2RA03803J

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