*Storage: Keep in dark place,Sealed in dry,Room Temperature.
*Shipping:
L-Ascorbic Acid is a natural antioxidant that selectively inhibits Cav3.2 channels (IC50=6.5 μM) and selectively damages cancer cells through reactive oxygen species (ROS) production, showing anticancer potential. Additionally, it promotes collagen synthesis and is widely used in skincare and cancer research.
Synonyms: L-Ascorbate;Vitamin C;Ascorbic acid, L-Ascorbic acid
4.5
*For Research Use Only !
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Discovery of Polyphenolic Natural Products as SARS-CoV-2 Mpro Inhibitors for COVID-19
Krueger, Nadine ; Kronenberger, Thales ; Xie, Hang , et al. Pharmaceuticals,2023,16(2):190.
Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has forced the development of direct-acting antiviral drugs due to the coronavirus disease 2019 (COVID-19) pandemic. The main protease of SARS-CoV-2 is a crucial enzyme that breaks down polyproteins synthesized from the viral RNA, making it a validated target for the development of SARS-CoV-2 therapeutics. New chem. phenotypes are frequently discovered in natural goods. In the current study, we used a fluorogenic assay to test a variety of natural products for their ability to inhibit SARS-CoV-2 Mpro. Several compounds were discovered to inhibit Mpro at low micromolar concentrations It was possible to crystallize robinetin together with SARS-CoV-2 Mpro, and the X-ray structure revealed covalent interaction with the protease's catalytic Cys145 site. Selected potent mols. also exhibited antiviral properties without cytotoxicity. Some of these powerful inhibitors might be utilized as lead compounds for future COVID-19 research.
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Keywords: COVID-19 ; antivirals ; coronavirus ; covalent drugs ; dynamic light scattering ; inhibitors ; main protease ; natural products
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Purchased from AmBeed: 20554-84-1 ; 18524-94-2 ; 568-73-0 ; 989-51-5 ; 484-12-8 ; 86404-04-8 ; 491-70-3 ; 2752-65-0 ; 6147-11-1 ; 10083-24-6 ; 50-81-7 ; 2752-65-0 ; 522-12-3 ; 529-44-2 ; 529-53-3 ; 546-43-0 ; 501-36-0 ; 28957-04-2 ; 4674-50-4 ; 477-43-0 ; 553-21-9 ; 96829-58-2 ; 96574-01-5 ; 20283-92-5 ; 490-31-3 ; 17912-87-7 ; 520-31-0 ; 86404-04-8
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CAS No. : | 50-81-7 |
Formula : | C6H8O6 |
M.W : | 176.12 |
SMILES Code : | O=C1O[C@H]([C@@H](O)CO)C(O)=C1O |
Synonyms : |
L-Ascorbate;Vitamin C;Ascorbic acid, L-Ascorbic acid
|
MDL No. : | MFCD00064328 |
InChI Key : | CIWBSHSKHKDKBQ-JLAZNSOCSA-N |
Pubchem ID : | 54670067 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P264-P270-P271-P280-P301+P312+P330-P302+P352-P304+P340+P312-P305+P351+P338-P332+P313-P337+P313-P362-P403+P233-P405-P501 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.5 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 6.0 |
Num. H-bond donors | 4.0 |
Molar Refractivity | 35.12 |
TPSA ? Topological Polar Surface Area: Calculated from | 107.22 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | -0.31 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | -1.64 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | -1.41 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | -2.6 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | -1.15 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | -1.42 |
Log S (ESOL):? ESOL: Topological method implemented from | 0.23 |
Solubility | 301.0 mg/ml ; 1.71 mol/l |
Class? Solubility class: Log S scale | Highly soluble |
Log S (Ali)? Ali: Topological method implemented from | -0.1 |
Solubility | 140.0 mg/ml ; 0.793 mol/l |
Class? Solubility class: Log S scale | Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | 1.49 |
Solubility | 5460.0 mg/ml ; 31.0 mol/l |
Class? Solubility class: Log S scale | Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg | High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg | No |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) | No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) | No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) | No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) | No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) | No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) | No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from | -8.54 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from | 0.0 |
Ghose? Ghose filter: implemented from | None |
Veber? Veber (GSK) filter: implemented from | 0.0 |
Egan? Egan (Pharmacia) filter: implemented from | 0.0 |
Muegge? Muegge (Bayer) filter: implemented from | 1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat | 0.56 |
PAINS? Pan Assay Interference Structures: implemented from | 0.0 alert |
Brenk? Structural Alert: implemented from | 0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from | No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) | 3.47 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39% | Stage #1: With Geobacillus stearothermophilus Tc-62 cyclomaltodextrin glucanotransferase In water at 55℃; for 50 h; Enzymatic reaction Stage #2: With glucoamylase GLUCZYM AF6 In water for 24 h; Enzymatic reaction | Test samples 10 to 15, having mutually different purities of ascorbic acid 2-glucoside as shown in Table 3, were prepared from an aqueous solution containing L-ascorbic acid and dextrin. Four parts by weight of "PINEDEX 100", a product name of a dextrin commercialized by Matsutani Chemical Industries Co., Ltd., Hyogo, Japan, was dissolved in 15 parts by weight of water by heating. Then, three parts by weight of L-ascorbic acid was admixed with the solution. Successively, the solution was admixed with 100 units/g dextrin, d.s.b., of a CGTase derived from Geobacillus stearothermophilus Tc-62 strain and 250 units/g dextrin, d.s.b., of an isoamylase specimen, commercialized by Hayashibara Biochemical Laboratories, Inc., Okayama, Japan, and subjected to an enzymatic reaction while keeping the solution at a pH of 5.5 and a temperature of 55°C for 50 hours to form ascorbic acid 2-glucoside. In addition, it can be speculated that α-glycosyl-L-ascorbic acids such as 2-O-α-maltosyl-L-ascorbic acid, 2-O-a-maltotriosyl-L-ascorbic acid, 2-O-α-maltotetraosyl-L-ascorbic acid, etc., would have been naturally formed in the reaction solution. After inactivating the remaining enzymes by heating, the reaction solution was adjusted to pH 4.5, admixed with 50 units/g dextrin, d.s.b., of "GLUCZYM AF6", a product name of a glucoamylase specimen commercialized by Amano Enzymes Inc., Aichi, Japan, and subjected to an enzymatic reaction for 24 hours for hydrolyzing the above α-glycosyl-L-ascorbic acids up to ascorbic acid 2-glucoside and hydrolyzing the remaining concomitant oligosaccharides up to D-glucose. At this stage, the reaction solution contained ascorbic acid 2-glucoside in a production yield of 39percent. The reaction solution was heated to inactivate glucoamylase, decolored with an activated charcoal, filtered, subjected to a column of a cation-exchange resin (H+-form) for desalting, and then subjected to an anion-exchange resin (OH--form) to absorb L-ascorbic acid and ascorbic acid 2-glucoside, followed by washing the resin with water to remove D-glucose and feeding 0.5 N hydrochloric acid solution to effect elution. The eluate was concentrated to give a solid content of about 50percent and then subjected to a column chromatography using "DOWEX 50WX4" (Ca2+-form), a product name of a strong-acid cation exchange resin commercialized by Dow Chemical Company. The concentrate was loaded on the column in a volume of about 1/50-fold of the wet resin volume, followed by feeding to the column refined water in a volume of 50-folds of the load volume of the concentrate at a linear velocity of 1 m/hour and fractionating the resulting eluate by 0.05-volume aliquots of the column volume. Thereafter, the composition of each fraction was measured on HPLC described in Experiment 1-2, and six fractions with an ascorbic acid 2-glucoside content of at least 80percent, d.s.b., were concentrated in vacuo to give respective solid concentrations of about 76percent. The resulting concentrates were respectively placed in a crystallizer, admixed with Test sample 1 in Experiment 1-1, as a seed crystal, in a content of two percent of each of the solid contents, d.s.b., followed by unforcedly cooling each concentrate from 40°C to 15°C over about two days while stirring gently to precipitate anhydrous crystalline ascorbic acid 2-glucoside. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid; at 18 - 35℃;Inert atmosphere; | (1) 100 ml (about 184 g) 99-99.5% sulfuric acid was added to 250 ml four-neck flask with stirring, 35 g of palmitic acid was added at 30-35C dissolved with stirring for 0.5-1 hour. The temperature was dropped to 20-25C under protection of nitrogen, 17.6 grams of vitamin C was added with stirring, and stirring was stopped until completely dissolved, and insulated at 18-20C for 48 hours to obtain reaction liquid vitamin C palmitate. (2) The temperature was controlled to below 40C , the reaction solution was slowly poured into 200 ml 4-neck flask placed in ice-bath containing 200 ml cooling water. 700 ml of toluene was added and then subjected to extraction, heated to 60C and cooled naturally with stirring, when the temperature of the system was reduced to about 40C, stratified, and lower waste acid was separated leaving the toluene layer. (3) To the toluene layer 30-35 200 ml of water was added, stirred at 30-35C for 3 hours, crystallized at 30-35C for three hours, cooled in ice-water at 10-15C, stirred for one hour and filtered. The filter cake was washed with 50 ml of toluene, and then washed with 500 ml of water at 30-35C. (4) The filter cake was added to 500 ml water at 30-35C for 1 hour, filtered, and then washed with 200 ml water at 30-35C and the effluent water PH =7 was drained, discharged, and air-dried at room temperature for one day to constant weight. The crude product of vitamin C palmitate 33-34 g was obtained. Yield of 79.7-82.1%. (5) Take the above crude vitamin C palmitate, dissolved in 7.5 times the volume of 95% ethanol at 35-40 deg. C, filtered, washed with 0.5 volume of 95% ethanol and filtrate had crystallized, heated at 35-40C until fully dissolved and transferred to 500 ml 4-neck flask, rapidly cooled to -25--20C, crystallized by stirring for 3 hours, filtered, the filter cake was washed with 95% cold ethanol and vacuum-dried at 40-50C for 8 hours to obtain 30-31 g of product. Yield 90-92%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tetrahydrofuran; at 20℃; for 12h; | 10.0 mg of the compound of the formula (I) was suspended in 0.5 mL of tetrahydrofuran and added L-ascorbic acid was added, and the reaction was stirred at room temperature for 12 hours. The resulting salt was amorphous. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91.3% | (1)500g of concentrated sulfuric acid was added to the three-necked flask, add 50g of palmitic acid, stirring to dissolve Solution in concentrated sulfuric acid was added 50gL- ascorbic acid, 18 C reaction 15h; (2)50g palmitic anhydride was added to the reaction mixture, the temperature was raised to 28 C, the reaction 20h, then After adding 10g of activated carbon and stirred for 15min; (3)The step (2) in the resulting mixture is added to 1250ml10 C cold water, filtered The filter cake is too crude, the crude product was rinsed with 100ml water, then washed with water after the crude product was dissolved in 750ml of butyl acetate, 50 C incubation decolorization 30min. Filtered and allowed to stand, stratification, the upper organic layer (Product containing layer) 50 C, washed twice with water, water per 500ml. After washing to the water layer, The organic layer was distilled off under reduced pressure to 400ml of butyl acetate, allowed to stand for cooling to 15 C, the solid was filtered off with 50ml The resulting solid was rinsed with ethyl acetate, drained, placed in a vacuum drying oven at 50 C. L-ascorbic acid-6-palmitate was obtained as a white flake with a purity of 98. 1% and a yield of 91.3%. |
Tags: 50-81-7 synthesis path| 50-81-7 SDS| 50-81-7 COA| 50-81-7 purity| 50-81-7 application| 50-81-7 NMR| 50-81-7 COA| 50-81-7 structure
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