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.
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http://dx.doi.org/10.3390/molecules28010238 | DOI Listing |
Fitoterapia
December 2024
Graduate School of Pharmaceutical Sciences, Tokushima University, Tokushima 770-8505, Japan. Electronic address:
Previously undescribed benzophenone rhamnosides, triadenosides A-F (1-6), were isolated from the aerial parts of Triadenum japonicum (Blume) Makino (Hypericaceae), where known compounds including benzophenone rhamnosides (7 and 8), benzophenone C-glucoside (9), flavonols and their glycosides (10-17), and biflavone (18) were also isolated and identified. Detailed spectroscopic analysis revealed that triadenoside A (1) was 2,3',5'-trihydroxy-4,6-dimethoxybenzophenone 2-O-α-L-rhamnopyranoside, while the absolute configuration of the rhamnosyl moiety was confirmed by HPLC analysis. Triadenosides B-E (2-5) were assigned as acetyl derivatives of 1 in their rhamnosyl moieties.
View Article and Find Full Text PDFJ Am Chem Soc
December 2024
Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
Photochemical deracemization has emerged as one of the most straightforward approaches to access highly enantioenriched compounds in recent years. While excited-state events such as energy transfer, single electron transfer, and ligand-to-metal charge transfer have been leveraged to promote stereoablation, approaches relying on hydrogen atom transfer, which circumvent the limitations imposed by the triplet energy and redox potential of racemic substrates, remain underexplored. Conceptually, the most attractive method for tertiary stereocenter deracemization might be hydrogen atom abstraction followed by hydrogen atom donation.
View Article and Find Full Text PDFChemistry
December 2024
Department of Chemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
The dimeric calcium and magnesium hydrides, [(BDI)AeH] [BDI=HC{(Me)CNDipp}, Dipp=2,6-i-PrCH; Ae=Mg or Ca] do not react with PhGeH in non-coordinating solvent. Addition of THF, however, induces deprotonation and access to monomeric Ae-germanide complexes, [(BDI)Ae{GePh}(THF)], both of which have been structurally characterized. Although this process is facile when Ae=Ca, the analogous magnesium-based reaction requires heating to temperatures >100 °C, under which conditions germanide formation is complicated by THF ring opening and the generation of an alkaline earth germyl-C-terminated n-butoxide, [(BDI)Mg{μ-O(CH)GePh}].
View Article and Find Full Text PDFFront Microbiol
November 2024
College of Life Science, Shandong Normal University, Jinan, China.
ACS Appl Bio Mater
November 2024
Institute of Chemistry and Biochemistry, Freie Universitaet Berlin, Takustr. 3, 14195 Berlin, Germany.
Thermoresponsive polymer coatings on cell culture substrates enable noninvasive cell detachment and cell sheet fabrication for biomedical applications. Optimized coatings should support controlled culture and detachment of various cell types and allow chemical modifications, e.g.
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