A specific molecular target for Neoamygdalin has not been identified. Its pharmacological activity is primarily attributed to the hydrogen cyanide (HCN) released upon hydrolysis of its cyanogenic glycoside structure by β-glucosidase, which can inhibit cytochrome C oxidase and other enzymes.

Neoamygdalin is generally considered a less active or inactive epimer compared to its isomer amygdalin. Its presence in some preparations has been regarded as a confounding factor leading to negative results in cytotoxicity studies of plant extracts.

Specific in vivo efficacy data for Neoamygdalin is limited. Its in vivo effects are largely derived from the release of cyanide by gut microbiota following oral administration. After oral administration of amygdalin (which contains components that epimerize to Neoamygdalin) in mice, peak cyanide concentrations in plasma were reached in approximately 1.5 to 2 hours.

A cytotoxicity protocol is as follows: Log-phase human cancer cells (e.g., SNU-C4) are seeded into 96-well plates (1×10⁴ cells/well) and cultured overnight. After removing the medium, fresh medium containing various concentrations of Neoamygdalin is added. Following 24 hours of treatment, the supernatant is discarded, and MTT solution is added to each well for 4 hours. Finally, DMSO is added to dissolve the formazan crystals, and the absorbance is measured spectrophotometrically at 570 nm.

An acute toxicity study in Kunming mice (6-8 weeks old, 18-22g, half male/female) is as follows: Neoamygdalin is suspended with 0.5% sodium carboxymethyl cellulose at different concentrations. After 12 hours of fasting, the suspension is administered orally (10 mL/kg body weight). Following administration, the animals are observed for 7 days to record any signs of toxicity and mortality.

Absorption, Distribution and Excretion
Following oral administration of amygdalin to mice, peak cyanide concentrations were reached at approximately 1.5–2 hours, consistent with the concentration range following potassium cyanide administration. The ability of different gastrointestinal regions and tumor tissues to release cyanide from amygdalin was assessed. Low activity was observed in the stomach and upper small intestine, while significant amounts of cyanide were released from the lower small intestine and feces. There was considerable variability among mice. Metabolism/Metabolites Amygdalin is a chemical compound composed of glucose, benzaldehyde, and cyanide, the latter of which can be released by β-glucosidase or emulsifying enzymes. Although these enzymes are absent in mammalian tissues, the human gut microbiota appears to possess these or similar enzymes, which can promote cyanide release, leading to poisoning in humans. Therefore, oral administration of amygdalin may be up to 40 times more toxic than intravenous administration. …Plant glycosides are characterized by the production of cyanide, as well as sugars and aromatic aldehydes, upon enzymatic or acidic hydrolysis. A common example is amygdalin (gentiobiose + benzaldehyde + HCN), which is found in bitter almonds… An enzyme complex, an emulsifying enzyme, exists alongside the glycoside in plant tissues and catalyzes the hydrolysis of the glycoside, first to mandelinonitrile or p-hydroxymandelinonitrile, then to benzaldehyde or p-hydroxybenzaldehyde and HCN. The aldehydes are oxidized to the corresponding aromatic acids and excreted as peptide conjugates. …Many species of the genus Prunus contain… amygdalin, which can be hydrolyzed by emulsifying enzymes… This process does not occur in intact plants; HCN is only released when plant tissues are damaged or begin to decay. In the rumen of monogastric animals, the breakdown of glycosides generally occurs more readily or rapidly than in the digestive tract. Furthermore, small molecules can be absorbed in the rumen and rapidly enter the bloodstream. The breakdown of cyanogenic glycosides (such as amygdalin), for example, amygdalin from plants in the Rosaceae family. For more complete data on the metabolism/metabolites of amygdalin (9 in total), please visit the HSDB record page.

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Biological Half-Life
Plasma and urine concentrations of amygdalin, as well as whole blood concentrations of CN- and SCN-, were determined after intravenous (4.5 g/m²) and oral (500 mg tablets) administration of amygdalin to cancer patients. Following intravenous administration, a parent drug concentration as high as 1401 μg/ml was observed, while plasma CN- and serum SCN- concentrations did not increase. The plasma elimination of amygdalin best conformed to a two-compartment open model, with a mean distribution phase half-life of 6.2 min, a mean elimination phase half-life of 120.3 min, and a mean clearance rate of 99.3 ml/min. Following oral administration of amygdalin, plasma concentrations decreased significantly, with peak values below 525 ng/ml. Whole blood CN- concentrations increased to as high as 2.1 μg/ml. SCN-CONCN did not increase within a few days, remaining stable at a value as high as 38 μg/mL serum.

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Its pharmacokinetics closely relate to amygdalin. After oral administration in mice, peak cyanide concentration is reached in approximately 1.5 to 2 hours. Its metabolism relies on hydrolysis by gut microbiota β-glucosidase to release free cyanide. In cancer patients, amygdalin's distribution half-life is 6.2 minutes, and elimination half-life is 120.3 minutes after i.v. administration. Additionally, oral administration can be up to 40 times more toxic than i.v. due to gut microbiota-mediated cyanide release.

Its toxicity primarily results from cyanide release. Preclinical data show its oral acute toxicity: a 322 mg/kg LD50 in rats. Several studies have shown that a mixture containing amygdalin/neoamygdalin can be mutagenic. For humans, there is a risk of cyanide poisoning from consuming large amounts of unprocessed cyanogenic foods like bitter almonds.

[1]. Identification and Analysis of Amygdalin, Neoamygdalin and Amygdalin Amide in Different Processed Bitter Almonds by HPLC-ESI-MS/MS and HPLC-DAD. Molecules. 2017;22(9):1425.

New amygdalins have been reported in peach (Prunus persica), passion fruit (Passiflora edulis), and other organisms with relevant data. Amygdalin is a cyanogenic glycoside isolated from the seeds of almonds and other plants in the Rosaceae family. It can be converted to benzaldehyde, D-glucose, and hydrocyanic acid by plant emulsifying enzymes (a complex of glucosidase and nitrile hydrolase) or hydrochloric acid. (NCI04) A cyanogenic glycoside found in the seeds of Rosaceae plants.

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C20H27NO11

457.4285

457.158

29883-16-7

441462

White to off-white solid powder

223-226 °C

-2.7

7

12

7

32

638

11

O1[C@]([H])([C@@]([H])([C@]([H])([C@@]([H])([C@@]1([H])C([H])([H])O[C@@]1([H])[C@@]([H])([C@]([H])([C@@]([H])([C@@]([H])(C([H])([H])O[H])O1)O[H])O[H])O[H])O[H])O[H])O[H])O[C@]([H])(C#N)C1C([H])=C([H])C([H])=C([H])C=1[H]

XUCIJNAGGSZNQT-UUGBRMIUSA-N

InChI=1S/C20H27NO11/c21-6-10(9-4-2-1-3-5-9)30-20-18(28)16(26)14(24)12(32-20)8-29-19-17(27)15(25)13(23)11(7-22)31-19/h1-5,10-20,22-28H,7-8H2/t10-,11-,12-,13-,14-,15+,16+,17-,18-,19-,20-/m1/s1

(S)-2-phenyl-2-(((2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-((((2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)methyl)tetrahydro-2H-pyran-2-yl)oxy)acetonitrile

Neoamygdalin (S)-AmylgdalinL-Amylgdalin

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~218.61 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.47 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (5.47 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (5.47 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)