Synthesis and studies of calcium channel blocking and antioxidant activities of novel 4-pyridinium and/or N-propargyl substituted 1,4-dihydropyridine derivatives

Ruciņš, Mārtiņš; Kaldre, Dainis; Pajuste, Kārlis; Férnandes, Meg da Silva; Vicente, Joaquim A.F.; Klimavičiusa, Linda; Jaschenko, Elina; Kanepe, I.; Шестакова, И.; Plotniece, Māra; Gosteva, Marina; Sobolev, Arkadij; Jansone, Baiba; Muceniece, Ruta; Kluša, Vija; Plotniece, Aiva

doi:10.1016/j.crci.2013.07.003

Cited by 28 publications

(28 citation statements)

References 40 publications

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“…At the same time, it is worthwhile to stress the calcium channel blocking properties of AP-12, because it is known that dysregulated Ca 2+ homeostasis in AD patients may affect signaling processes and related pathways [3, 6]. Taking together, the memory enhancing and anxiolytic activities and the influence on brain protein expression obtained in the present study on Tg female mice and did not show a considerable sex specificity if compare with the previously found results in Tg male mice [11]. …”

Section: Discussionsupporting

confidence: 62%

“…The 1,4-dihydropyridine derivative AP-12 (3’,5’-bisethoxycarbonyl-2’,6’-dimethyl-1-dodecyl-1’,4-dihydro[3,4’]bipyridinyl-1-ium bromide), MW 579.61, was synthesized at the Latvian Institute of Organic Synthesis, Riga, Latvia and it has a purity of 98% according to high performance liquid chromatography [15]. For intraperitoneally (ip) injections, AP-12 was dissolved in saline (with 0.1% Tween and using ultrasonication).…”

Section: Methodsmentioning

confidence: 99%

“…For intraperitoneally (ip) injections, AP-12 was dissolved in saline (with 0.1% Tween and using ultrasonication). The dose of 1 mg/kg of AP-12 was chosen as that demonstrating anxiolytic and memory-enhancing effects obtained in our previous study using Tg APPSweDI male mice [11]. …”

Section: Methodsmentioning

confidence: 99%

“…This compound was also shown to cross the blood-brain barrier [10] and exert Ca 2+ antagonistic properties in neuroblastoma and in the vascular smooth muscle cell line [11]. …”

Section: Introductionmentioning

confidence: 99%

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Memory-enhancing and brain protein expression-stimulating effects of novel calcium antagonist in Alzheimer’s disease transgenic female mice

Jansone

Kadish

Groen

et al. 2016

Pharmacological Research

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The prevalence of Alzheimer’s disease (AD) is higher in females than in males, and causes more severe cognitive, memory and behavioral impairments. Previously, in male transgenic (Tg) APPSweDI mice, we reported that the novel lipophilic 1,4-dihydropyridine (DHP) derivative AP-12 crossed the blood-brain barrier, blocked neuronal and vascular calcium channels, changed brain protein expression and improved behavior. In this study, we used female Tg APPSweDI mice to assess the effects of AP-12 on behavior, and brain protein expression, with a particular focus on those of the GABAergic system. The results showed that in female Tg mice, similar to male Tg mice, AP-12 improved spatial learning/memory performance in the water maze test and demonstrated anxiolytic effect in the elevated zero maze (after single administration of AP-12) and elevated plus maze (after chronic injections of AP-12). In addition, we demonstrated upregulated expression of glutamate decarboxylase 67 (GAD67) and vesicular GABA transporter (VGAT) in the cingulate cortex and hippocampus, pointing to the role of the GABAergic system as one of the neural networks dysregulated in AD. In both female and male mice, AP-12 did not change the expression of hippocampal Homer-1, a protein which is involved in synaptic plasticity. However, in cingulate cortex, the staining density of Homer-1 was significantly increased in female mice. Further, female mice (similar to male mice) did not show changes in brain AChE expression and in the amyloid beta load in the hippocampus and cingulate cortex. In conclusion, the memory enhancing, anxiolytic and protein expression effects of AP-12 did not show sex specificity in APPSweDI mice. Considering the ability of AP-12 to block brain calcium channels and improve memory by enhancing the GABAergic and synaptic plasticity processes, AP-12 is a promising compound which merits further pre-clinical studies to investigate its usefulness in the treatment of AD.

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Section: Discussionsupporting

confidence: 62%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…This compound was also shown to cross the blood-brain barrier [10] and exert Ca 2+ antagonistic properties in neuroblastoma and in the vascular smooth muscle cell line [11]. …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Memory-enhancing and brain protein expression-stimulating effects of novel calcium antagonist in Alzheimer’s disease transgenic female mice

Jansone

Kadish

Groen

et al. 2016

Pharmacological Research

Self Cite

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“…They are used as solvents, catalysts, and reagents in a variety of organic transformations [6,7]. Moreover, pyridinium salts have been identified as potent cytotoxic agents and have been used extensively in the dental profession for the treatment of oral infections [8][9][10][11]. However, high cost, tedious purification procedure of the product, as well as moisture sensitivity and decomposition of some pyridinium salts under normal atmospheric conditions, have restricted their widespread practical application on the industrial scale.…”

Section: Introductionmentioning

confidence: 98%

A straightforward route for covalently anchored pyridinium salt onto upper rim of c-methylcalix[4]resorcinarene with selective antibacterial activity against Gram-positive bacteria

et al. 2015

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In this research, we report a straightforward route for the synthesis of a cationic supramolecular structure via covalently anchoring an ionic liquid-containing pyridinium moiety onto c-methylcalix[4]resorcinarene. Antibacterial activity of the new functionalized c-methylcalix[4]resorcinarene was evaluated against Gram-positive and Gram-negative bacteria. Surprisingly, this compound exhibited a selective antibacterial effect on Gram-positive bacteria, which is very important from the industrial and medicinal point of view. These preliminary results are attractive for the development of a new antibacterial agent. Electronic supplementary material The online version of this article (

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Solvent‐free Synthesis of Water‐Soluble New Pyridinium Amines: Spectroscopic Characterization, Biological Screening, and Interaction Study with DNA

Zafar

Masood

Nazar

et al. 2017

J Chinese Chemical Soc

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New water‐soluble pyridinium amines (2–8) were obtained by the solid‐state reactions of 4‐chloro‐1‐methylpyridin‐1‐ium triflate (1) and various primary aromatic amines. These compounds were characterized by 1H, 13C NMR, FTIR, UV–vis, and fluorescence spectroscopic methods along with single‐crystal X‐ray structure determination. The interaction potentials of all newly synthesized compounds with calf thymus DNA (CT‐DNA) were investigated by UV–vis and florescence spectroscopy accompanied by docking studies. UV–vis spectroscopy indicated that the binding of compounds with CT‐DNA takes place via the intercalative mode. The compounds were also screened for their potential as antioxidants and enzyme inhibition agents. Some compounds displayed excellent butyrylcholine and acetylcholine esterase inhibition activities and were effective in scavenging the 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical in a dose‐dependent manner comparable to a standard.

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Synthesis and studies of calcium channel blocking and antioxidant activities of novel 4-pyridinium and/or N-propargyl substituted 1,4-dihydropyridine derivatives

Cited by 28 publications

References 40 publications

Memory-enhancing and brain protein expression-stimulating effects of novel calcium antagonist in Alzheimer’s disease transgenic female mice

Memory-enhancing and brain protein expression-stimulating effects of novel calcium antagonist in Alzheimer’s disease transgenic female mice

A straightforward route for covalently anchored pyridinium salt onto upper rim of c-methylcalix[4]resorcinarene with selective antibacterial activity against Gram-positive bacteria

Solvent‐free Synthesis of Water‐Soluble New Pyridinium Amines: Spectroscopic Characterization, Biological Screening, and Interaction Study with DNA

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