2-Propargylamino-naphthoquinone derivatives as multipotent agents for the treatment of Alzheimer’s disease

Mezeiová, Eva; Janočková, Jana; Andrýs, Rudolf; Soukup, Ondřej; Kobrlová, Tereza; Múčková, Lubica; Pejchal, Jaroslav; Šimunková, Miriama; Handl, Jiří; Micankova, Petra; Čapek, Jan; Roušar, Tomáš; Hrabinová, Martina; Nepovimová, Eugenie; Marco‐Contelles, José; Valko, Marián; Korábečný, Jan

doi:10.1016/j.ejmech.2020.113112

Cited by 23 publications

(11 citation statements)

References 44 publications

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“…MAO inhibition assay was performed as previously described [ 51 ]. Supplementary Materials provides details of this assay.…”

Section: Methodsmentioning

confidence: 99%

“…The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetraziolium bromide (Sigma–Aldrich) reduction assay was used for measurement of the compounds’ cytotoxicity, according to Mosmann [ 51 ]. MTT is a water-soluble tetrazolium salt that is converted to purple formazan by succinate dehydrogenase in mitochondria of viable cells [ 52 , 53 ].…”

Section: Methodsmentioning

confidence: 99%

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Amaryllidaceae Alkaloids of Norbelladine-Type as Inspiration for Development of Highly Selective Butyrylcholinesterase Inhibitors: Synthesis, Biological Activity Evaluation, and Docking Studies

Mamun

Pidaný

Hulcová

et al. 2021

IJMS

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Alzheimer’s disease (AD) is a multifactorial neurodegenerative condition of the central nervous system (CNS) that is currently treated by cholinesterase inhibitors and the N-methyl-d-aspartate receptor antagonist, memantine. Emerging evidence strongly supports the relevance of targeting butyrylcholinesterase (BuChE) in the more advanced stages of AD. Within this study, we have generated a pilot series of compounds (1–20) structurally inspired from belladine-type Amaryllidaceae alkaloids, namely carltonine A and B, and evaluated their acetylcholinesterase (AChE) and BuChE inhibition properties. Some of the compounds exhibited intriguing inhibition activity for human BuChE (hBuChE), with a preference for BuChE over AChE. Seven compounds were found to possess a hBuChE inhibition profile, with IC50 values below 1 µM. The most potent one, compound 6, showed nanomolar range activity with an IC50 value of 72 nM and an excellent selectivity pattern over AChE, reaching a selectivity index of almost 1400. Compound 6 was further studied by enzyme kinetics, along with in-silico techniques, to reveal the mode of inhibition. The prediction of CNS availability estimates that all the compounds in this survey can pass through the blood-brain barrier (BBB), as disclosed by the BBB score.

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“…MAO inhibition assay was performed as previously described [ 51 ]. Supplementary Materials provides details of this assay.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Amaryllidaceae Alkaloids of Norbelladine-Type as Inspiration for Development of Highly Selective Butyrylcholinesterase Inhibitors: Synthesis, Biological Activity Evaluation, and Docking Studies

Mamun

Pidaný

Hulcová

et al. 2021

IJMS

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“…Naphthoquinone is one of the most studied pharmacophore groups in medicinal chemistry and it is known to be present in the molecular structure of many natural and synthetic bioactive compounds. [1][2][3] Compounds containing naphthoquinone moiety exhibit a wide range of pharmacological activities such as anti-inflammatory, [4,5] antimicrobial, [6][7][8] antiviral, [9] antimalarial, [10] and anticancer [11,12] as well as DNA cleavage activity. [13] In recent years, studies have been conducted in which various naphthoquinone derivatives have been synthesized for the treatment of Alzheimer's, and their activities on enzymes associated with this disease have been investigated.…”

Section: Introductionmentioning

confidence: 99%

Anti‐inflammatory Potential of 1,4‐Naphthoquinone Acyl Thiourea Hybrids on Lipopolysaccharide‐Activated Mammalian Macrophages, and Their Acid Dissociation Constants

Canatar,

Türkben,

Efeoglu

et al. 2023

ChemistrySelect

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In this study, seven new and known 1,4‐naphthoquinone acyl thiourea hybrids were synthesized and their molecular structures were confirmed by various analytical methods. These derivatives were tested for their anti‐inflammatory potential on the murine macrophages. Pro‐inflammatory cytokine production levels and cell viabilities were compared between the groups and with LPS positive control groups to determine the most potent anti‐inflammatory drug candidate. Our results suggest that these derivatives had anti‐inflammatory activity without exerting major cytotoxicity. Their future evaluation in inflammatory and autoimmune disease settings will be crucial for their possible utilization in the clinical setting. The acid dissociation constants of synthesized hybrids 1–7 were determined potentiometrically at 25.0±0.1 °C, at an ionic strength of 0.1 M NaCl in 20 % (v/v) DMSO – water hydro‐organic solvent mixture in an acidic medium. Three acid dissociation constants were calculated for each hybrid with the HYPERQUAD computer program using the data obtained as a result of potentiometric titrations under the specified conditions.

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“…Propargylamine is the key intermediates in several kinds of chemicals and biologically active molecules such as Parkinson's disease. [1][2][3] Different propargylamines are usually synthesized by the three-component coupling method (A 3 coupling) of amine, alkyne and aldehyde. [4][5][6][7][8][9][10][11][12][13][14] In AHA coupling reactions, halomethane is an inexpensive and readily available industrial solvent as a methylene fragment for replacing aldehydes.…”

Section: Introductionmentioning

confidence: 99%

“…Propargylamine is the key intermediates in several kinds of chemicals and biologically active molecules such as Parkinson's disease [1–3] . Different propargylamines are usually synthesized by the three‐component coupling method (A 3 coupling) of amine, alkyne and aldehyde [4–14] .…”

Section: Introductionmentioning

confidence: 99%

Atomically Precise Cu_n(n=3, 6 and 11) Nanocatalysts for Alkyne‐Haloalkane‐Amine (AHA) Coupling Reaction

et al. 2022

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Ultrafine nanoclusters with precise structure as catalysts are of particular interest due to high sites density, high metal atomic efficiency and potentially favorable metal-support interactions. In this work, we used a simple wet impregnation method to fix three Cu n (n = 3, 6, 11) nanoclusters (NCs) on activated carbon (AC). The structural characteristics of the three obtained Cu n (n = 3, 6, 11)/AC catalysts were analyzed by FT-IR, XRD, TEM and XPS. Cu n (n = 3, 6, 11)/AC catalysts are used for exploring catalytic performance of alkyne-haloalkane-amine (AHA) coupling reaction. The results show that Cu n (n = 3, 6, 11)/AC catalysts exhibited better catalytic activity for AHA coupling reaction than Cu salt and other non-noble metal catalysts, with TON up to 715.4. This work provides a new way to understand the relationship between structure and catalytic performance of ultra-small copper NCs.

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2-Propargylamino-naphthoquinone derivatives as multipotent agents for the treatment of Alzheimer’s disease

Cited by 23 publications

References 44 publications

Amaryllidaceae Alkaloids of Norbelladine-Type as Inspiration for Development of Highly Selective Butyrylcholinesterase Inhibitors: Synthesis, Biological Activity Evaluation, and Docking Studies

Amaryllidaceae Alkaloids of Norbelladine-Type as Inspiration for Development of Highly Selective Butyrylcholinesterase Inhibitors: Synthesis, Biological Activity Evaluation, and Docking Studies

Anti‐inflammatory Potential of 1,4‐Naphthoquinone Acyl Thiourea Hybrids on Lipopolysaccharide‐Activated Mammalian Macrophages, and Their Acid Dissociation Constants

Atomically Precise Cu_n(n=3, 6 and 11) Nanocatalysts for Alkyne‐Haloalkane‐Amine (AHA) Coupling Reaction

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2-Propargylamino-naphthoquinone derivatives as multipotent agents for the treatment of Alzheimer’s disease

Cited by 23 publications

References 44 publications

Amaryllidaceae Alkaloids of Norbelladine-Type as Inspiration for Development of Highly Selective Butyrylcholinesterase Inhibitors: Synthesis, Biological Activity Evaluation, and Docking Studies

Amaryllidaceae Alkaloids of Norbelladine-Type as Inspiration for Development of Highly Selective Butyrylcholinesterase Inhibitors: Synthesis, Biological Activity Evaluation, and Docking Studies

Anti‐inflammatory Potential of 1,4‐Naphthoquinone Acyl Thiourea Hybrids on Lipopolysaccharide‐Activated Mammalian Macrophages, and Their Acid Dissociation Constants

Atomically Precise Cun(n=3, 6 and 11) Nanocatalysts for Alkyne‐Haloalkane‐Amine (AHA) Coupling Reaction

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Atomically Precise Cu_n(n=3, 6 and 11) Nanocatalysts for Alkyne‐Haloalkane‐Amine (AHA) Coupling Reaction