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Papers of the Week


January 27, 2023


Molecules


http://www.ncbi.nlm.nih.gov/pubmed/36615435?dopt=Abstract


28


1

Benzophenone Derivatives with Histamine H Receptor Affinity and Cholinesterase Inhibitory Potency as Multitarget-Directed Ligands for Possible Therapy of Alzheimer’s Disease.

Authors

Godyń J, Zaręba P, Stary D, Kaleta M, Kuder KJ, Latacz G, Mogilski S, Reiner-Link D, Frank A, Doroz-Płonka A, Olejarz-Maciej A, Sudoł-Tałaj S, Nolte T, Handzlik J, Stark H, Więckowska A, Malawska B, Kieć-Kononowicz K, Łażewska D, Bajda M
Molecules. 2022 Dec 28; 28(1).
PMID: 36615435.

Abstract

The multitarget-directed ligands demonstrating affinity to histamine H 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 with a high affinity for HR ( = 8 nM) and significant inhibitory activity toward BuChE (IC = 172 nM and 1.16 µM for BuChE and BuChE, respectively). Further in vitro studies revealed that compound (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 (P) of 6.3 × 10 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 in the Passive Avoidance Test and the Formalin Test. While compound did not show a statistically significant influence on memory and learning, it showed analgesic properties in both acute (ED = 20.9 mg/kg) and inflammatory (ED = 17.5 mg/kg) pain.