Godyn_2022_Molecules_28_

Reference

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

Related information

Citations formats

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 (2022)
Benzophenone Derivatives with Histamine H(3) Receptor Affinity and Cholinesterase Inhibitory Potency as Multitarget-Directed Ligands for Possible Therapy of Alzheimer's Disease
Molecules 28 :

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 (2022)
Molecules 28 :

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    [paper] => Godyn_2022_Molecules_28_
    [author] => 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
    [year] => 2022
    [title] => Benzophenone Derivatives with Histamine H(3) Receptor Affinity and Cholinesterase Inhibitory Potency as Multitarget-Directed Ligands for Possible Therapy of Alzheimer's Disease
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            [content] => 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.
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