Bibliographic Details
| Title: |
Benzophenone Derivatives with Histamine H3 Receptor Affinity and Cholinesterase Inhibitory Potency as Multitarget-Directed Ligands for Possible Therapy of Alzheimer’s Disease |
| Authors: |
Justyna Godyń, Paula Zaręba, Dorota Stary, Maria Kaleta, Kamil J. Kuder, Gniewomir Latacz, Szczepan Mogilski, David Reiner-Link, Annika Frank, Agata Doroz-Płonka, Agnieszka Olejarz-Maciej, Sylwia Sudoł-Tałaj, Tobias Nolte, Jadwiga Handzlik, Holger Stark, Anna Więckowska, Barbara Malawska, Katarzyna Kieć-Kononowicz, Dorota Łażewska, Marek Bajda |
| Source: |
Molecules, Vol 28, Iss 1, p 238 (2022) |
| Publisher Information: |
MDPI AG, 2022. |
| Publication Year: |
2022 |
| Collection: |
LCC:Organic chemistry |
| Subject Terms: |
multitarget-directed ligands, benzophenone derivatives, Alzheimer’s disease, cholinesterase inhibitors, histamine H3 receptor ligands, Organic chemistry, QD241-441 |
| More Details: |
The multitarget-directed ligands demonstrating affinity to histamine H3 receptor and additional cholinesterase inhibitory potency represent a promising strategy for research into the effective treatment of Alzheimer’s disease. In this study, a novel series of benzophenone derivatives was designed and synthesized. Among these derivatives, we identified compound 6 with a high affinity for H3R (Ki = 8 nM) and significant inhibitory activity toward BuChE (IC50 = 172 nM and 1.16 µM for eqBuChE and hBuChE, respectively). Further in vitro studies revealed that compound 6 (4-fluorophenyl) (4-((5-(piperidin-1-yl)pentyl)oxy)phenyl)methanone) displays moderate metabolic stability in mouse liver microsomes, good permeability with a permeability coefficient value (Pe) of 6.3 × 10−6 cm/s, and its safety was confirmed in terms of hepatotoxicity in the HepG2 cell line. Therefore, we investigated the in vivo activity of compound 6 in the Passive Avoidance Test and the Formalin Test. While compound 6 did not show a statistically significant influence on memory and learning, it showed analgesic properties in both acute (ED50 = 20.9 mg/kg) and inflammatory (ED50 = 17.5 mg/kg) pain. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1420-3049 |
| Relation: |
https://www.mdpi.com/1420-3049/28/1/238; https://doaj.org/toc/1420-3049 |
| DOI: |
10.3390/molecules28010238 |
| Access URL: |
https://doaj.org/article/2481fe283dea45f89bc7efb49683033f |
| Accession Number: |
edsdoj.2481fe283dea45f89bc7efb49683033f |
| Database: |
Directory of Open Access Journals |
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