DMSO-mediated transformation of 3-amino-2-hydroxynaphthazarins to natural 2,3-dihydroxynaphthazarins and related compounds

Polonik, N. S.; Полоник, С. Г.

doi:10.1016/j.tetlet.2016.06.056

Cited by 6 publications

(5 citation statements)

References 34 publications

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“…Ethylspinazarin 4 (U-573) is readily prepared by conversion of the available ethyldichloroNQ 1 mixture of two isomeric nitroNQs 2a,b, subsequent reduction of ni-troNQs with sodium sulfide in aminoNQs 3a,b in water solution and acid-catalyzed transformation of aminoNQs in ethylspinazarin 4 (U-573) under DMSO action in water-formic acid solution at reflux (Scheme 1) [24,25]. The total yield of ethylspinazarin 4 (U-573) in the three stages was 62%.…”

Section: Synthesis Of 6-ethyl-2358-tetrahydroxy-14-naphthoquinone (Et...mentioning

confidence: 99%

“…6-Ethyl-2,3-dihydroxynaphthazarin 4 (U-573) was synthesized from ethyldichloronaphtazarin as described in our works [22,24]; 2-Hydroxy-3-ethylnaphthazarin 6 was obtained by reductive dechlorination of appropriate dichlorohydroxyethylnaphthazarin 5 according to our previous paper [26]; the synthesis of 3,4,6-tri-O-acetyl-α-d-glucopyranose 1,2-(tert-butoxy orthoacetate) 7 was accomplished using Kochetkov's method, as described in reference [26]; 2-Hydroxy-3-ethylnaphthazarin 6 was condensed with 3,4,6-tri-O-acetylα-d-glucopyranose 1,2-(tert-butoxyorthoacetate) 7 in chlorobenzene at reflux and led to acetylglucoside 8 (U-443) as described in our previous works [17,25]. NMR spectra for 4 (U-573) were recorded on a Bruker AVANCE-500 at frequencies 500 MHz for 1 H spectra and 125 MHz for 13 C in DMSO-d 6 .…”

Section: Synthesis Of 14-naphthoquinones Generalmentioning

confidence: 99%

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Protection Activity of 1,4-Naphthoquinones in Rotenone-Induced Models of Neurotoxicity

Agafonova,

Chingizova,

Chaikina

et al. 2024

Marine Drugs

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The MTS cell viability test was used to screen a mini library of natural and synthetic 1,4-naphthoquinone derivatives (1,4-NQs) from marine sources. This screening identified two highly effective compounds, U-443 and U-573, which showed potential in protecting Neuro-2a neuroblastoma cells from the toxic effects of rotenone in an in vitro model of neurotoxicity. The selected 1,4-NQs demonstrated the capability to reduce oxidative stress by decreasing the levels of reactive oxygen species (ROS) and nitric oxide (NO) in Neuro-2a neuroblastoma cells and RAW 264.7 macrophage cells and displayed significant antioxidant properties in mouse brain homogenate. Normal mitochondrial function was restored and the mitochondrial membrane potential was also regained by 1,4-NQs after exposure to neurotoxins. Furthermore, at low concentrations, these compounds were found to significantly reduce levels of proinflammatory cytokines TNF and IL-1β and notably inhibit the activity of cyclooxygenase-2 (COX-2) in RAW 264.7 macrophages. The results of docking studies showed that the 1,4-NQs were bound to the active site of COX-2, analogically to a known inhibitor of this enzyme, SC-558. Both substances significantly improved the behavioral changes in female CD1 mice with rotenone-induced early stage of Parkinson’s disease (PD) in vivo. It is proposed that the 1,4-NQs, U-443 and U-573, can protect neurons and microglia through their potent anti-ROS and anti-inflammatory activities.

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Section: Synthesis Of 6-ethyl-2358-tetrahydroxy-14-naphthoquinone (Et...mentioning

confidence: 99%

Section: Synthesis Of 14-naphthoquinones Generalmentioning

confidence: 99%

Protection Activity of 1,4-Naphthoquinones in Rotenone-Induced Models of Neurotoxicity

Agafonova,

Chingizova,

Chaikina

et al. 2024

Marine Drugs

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“…Naphthoquinone 64 reacted with sodium nitrite, forming intermediate 69, followed by a reduction producing 3-amino-2-hydroxynaphthazarines (70) [144]. Naphthoquinones 70 then underwent dimethylsulfoxide-mediated oxidation [145,146]. 2-hydroxy-6,7-dimethylnaphthazarine (71) was prepared by oxidation 64a with MnO 2 in concentrated acid, while 6,7-dichloro-2-hydroxy-naphthazarine (72) was produced by a nucleophilic substitution of chlorine atoms by methyl groups, but the reaction conditions were not described [147].…”

Section: Naphthoquinones With Activity Against Pdmentioning

confidence: 99%

Naphthoquinones as a Promising Class of Compounds for Facing the Challenge of Parkinson’s Disease

Santos,

de Moraes,

Pacheco

et al. 2023

Pharmaceuticals

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Parkinson’s disease (PD) is a degenerative disease that affects approximately 6.1 million people and is primarily caused by the loss of dopaminergic neurons. Naphthoquinones have several biological activities explored in the literature, including neuroprotective effects. Therefore, this review shows an overview of naphthoquinones with neuroprotective effects, such as shikonin, plumbagin and vitamin K, that prevented oxidative stress, in addition to multiple mechanisms. Synthetic naphthoquinones with inhibitory activity on the P2X7 receptor were also found, leading to a neuroprotective effect on Neuro-2a cells. It was found that naphthazarin can act as inhibitors of the MAO-B enzyme. Vitamin K and synthetic naphthoquinones hybrids with tryptophan or dopamine showed inhibition of the aggregation of α-synuclein. Synthetic derivatives of juglone and naphthazarin were able to protect Neuro-2a cells against neurodegenerative effects of neurotoxins. In addition, routes for producing synthetic derivatives were also discussed. With the data presented, 1,4-naphthoquinones can be considered as a promising class in the treatment of PD and this review aims to assist the scientific community in the application of these compounds. The derivatives presented can also support further research that explores their structures as synthetic platforms, in addition to helping to understand the interaction of naphthoquinones with biological targets related to PD.

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“…Naphthazarin (Fluka) (1) was recrystallized from ethanol, while 2-hydroxynaphthazarin (naphthopurpurin) (2), 2-hydroxy-3-methylnaphthazarin (3) and 2-hydroxy-3-ethylnaphthazarin (4) were prepared according with Anufriev's paper [54]; 2,3-Dihydroxynaphthazarin (5), 2,3-dihydroxy-6-methynaphthazarin (6), 6-ethyl-2,3-dihydroxynaphthazarin (7) and spinochrome D (8) were obtained according the the method described in our previous papers [55,56]; 2,3,6-Trihydroxy-7-ethylnaphthazarin (echinochrome A) (9) was isolated from sea urchins Scaphechinus mirabilis; 3,4,6-Tri-O-acetyl-α-d-glucopyranose 1,2-(tert-butoxy orthoacetate) 11 was prepared according to a method described in [57]; 2-Hydroxy-6,7-dimethylnaphthazarin (22) and 6,7-dichloro-2-hydroxynaphthazarin (23) were prepared according to a method described in [14]; 2-Hydroxy-7-methoxynaphthazarin (24) and 2-hydroxy-6,7-dimethoxynaphthazarin (25) were prepared as described in our previous work [58]. Tetra-O-acetyl-1-thio-β-d-glucopyranose (27), tetra-O-acetyl-1-thio-β-d-galactopyranose (53), tetra-O-acetyl-1-thio-β-d-mannopyranose (54), tri-O-acetyl-1-thio-β-d-xylopyranose (55) were prepared as described in [59].…”

Section: General Chemistry (Reagents Solvents and Equipment)mentioning

confidence: 99%

Synthesis, Cytotoxic Activity Evaluation and Quantitative Structure-ActivityAnalysis of Substituted 5,8-Dihydroxy-1,4-naphthoquinones and Their O- and S-Glycoside Derivatives Tested against Neuro-2a Cancer Cells

et al. 2020

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Based on 6,7-substituted 2,5,8-trihydroxy-1,4-naphtoquinones (1,4-NQs) derived from sea urchins, five new acetyl-O-glucosides of NQs were prepared. A new method of conjugation of per-O-acetylated 1-mercaptosaccharides with 2-hydroxy-1,4-NQs through a methylene spacer was developed. Methylation of 2-hydroxy group of quinone core of acetylthiomethylglycosides by diazomethane and deacetylation of sugar moiety led to 28 new thiomethylglycosidesof 2-hydroxy- and 2-methoxy-1,4-NQs. The cytotoxic activity of starting 1,4-NQs (13 compounds) and their O- and S-glycoside derivatives (37 compounds) was determined by the MTT method against Neuro-2a mouse neuroblastoma cells. Cytotoxic compounds with EC50 = 2.7–87.0 μM and nontoxic compounds with EC50 > 100 μM were found. Acetylated O- and S-glycosides 1,4-NQs were the most potent, with EC50 = 2.7–16.4 μM. Methylation of the 2-OH group innaphthoquinone core led to a sharp increase in the cytotoxic activity of acetylated thioglycosidesof NQs, which was partially retained for their deacetylated derivatives. Thiomethylglycosides of 2-hydroxy-1,4-NQs with OH and MeO groups in quinone core at positions 6 and 7, resprectively formed a nontoxic set of compounds with EC50 > 100 μM. A quantitative structure-activity relationship (QSAR) model of cytotoxic activity of 22 1,4-NQ derivatives was constructed and tested. Descriptors related to the cytotoxic activity of new 1,4-NQ derivatives were determined. The QSAR model is good at predicting the activity of 1,4-NQ derivatives which are unused for QSAR models and nontoxic derivatives.

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DMSO-mediated transformation of 3-amino-2-hydroxynaphthazarins to natural 2,3-dihydroxynaphthazarins and related compounds

Cited by 6 publications

References 34 publications

Protection Activity of 1,4-Naphthoquinones in Rotenone-Induced Models of Neurotoxicity

Protection Activity of 1,4-Naphthoquinones in Rotenone-Induced Models of Neurotoxicity

Naphthoquinones as a Promising Class of Compounds for Facing the Challenge of Parkinson’s Disease

Synthesis, Cytotoxic Activity Evaluation and Quantitative Structure-ActivityAnalysis of Substituted 5,8-Dihydroxy-1,4-naphthoquinones and Their O- and S-Glycoside Derivatives Tested against Neuro-2a Cancer Cells

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