Kuder KJ

References (1)

Title : Benzophenone Derivatives with Histamine H(3) Receptor Affinity and Cholinesterase Inhibitory Potency as Multitarget-Directed Ligands for Possible Therapy of Alzheimer's Disease - Godyn_2022_Molecules_28_
Author(s) : Godyn J , Zareba P , Stary D , Kaleta M , Kuder KJ , Latacz G , Mogilski S , Reiner-Link D , Frank A , Doroz-Plonka A , Olejarz-Maciej A , Sudol-Talaj S , Nolte T , Handzlik J , Stark H , Wieckowska A , Malawska B , Kiec-Kononowicz K , Lazewska D , Bajda M
Ref : Molecules , 28 : , 2022
Abstract : The multitarget-directed ligands demonstrating affinity to histamine H(3) 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 H(3)R (K(i) = 8 nM) and significant inhibitory activity toward BuChE (IC(50) = 172 nM and 1.16 microM 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 (P(e)) of 6.3 x 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 (ED(50) = 20.9 mg/kg) and inflammatory (ED(50) = 17.5 mg/kg) pain.
ESTHER : Godyn_2022_Molecules_28_
PubMedSearch : Godyn_2022_Molecules_28_
PubMedID: 36615435