- Sortase A (SrtA) of Staphylococcus aureus: Mandelic acid inhibits SrtA activity with an IC50 of 66.15 ± 24.39 μg/mL, binding tightly to residues Pro-163, Val-166, Gly-167, Val-168, Ile-199 and Leu-169 via intermolecular forces, inducing conformational changes that reduce enzyme activity.
- Aldo‑keto reductase family 1 member B1 (AKR1B1): The (S)-isomer of mandelic acid exhibits affinity for AKR1B1 with a Ki of 100 μM.
- Tyrosinase: Mandelic acid acts as a tyrosinase inhibitor, blocking the enzyme that stimulates melanin production, thereby contributing to skin brightening effects.

- Mandelic acid exhibits significant sperm-immobilizing effects in a concentration-dependent manner. Within 20 seconds, mandelic acid induced sperm immobilization with a minimum effective concentration of 0.86 mg/mL and a median effective concentration of 0.54 mg/mL. Plasma membrane disruptions were relatively mild, but mitochondrial depolarization occurred.
- Mandelic acid is an antimicrobial agent. Its minimum inhibitory concentration to inhibit 50% of clinical S. aureus isolates (MIC50) was 20 mg/mL, the MIC90 was 40 mg/mL, the minimum bactericidal concentration to kill 50% of strains (MBC50) was 20 mg/mL, and the MBC90 was 80 mg/mL.
- Mandelic acid inhibits the activity of S. aureus sortase A (SrtA) with an IC50 of 66.15 ± 24.39 μg/mL. Molecular docking studies revealed that mandelic acid binds tightly to the active center of SrtA via various intermolecular forces, resulting in a conformational change that reduces enzyme activity.
- In the presence of rat hepatocytes, S-mandelic acid undergoes chiral inversion to R-mandelic acid. However, mandelic acid enantiomers remained unchanged in acidic and neutral phosphate buffers, HepG2 cells, and intestinal flora, suggesting that the inversion is mediated by hepatic metabolic enzymes.
- (S)-Mandelic acid undergoes chiral inversion when incubated with intestinal bacteria of Sprague-Dawley rats for 24 hours, converting to (R)-glycolic acid, and also undergoes inversion when co-incubated with rat hepatocytes for 2 hours.

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Mandelic acid ((±)-mandelic acid) shows promise as a non-surfactant spermicide in the future because it produces minor damage to the plasma membrane and significantly immobilizes sperm [1]. The hydrolysis of bitter almond extract yields mandelic acid, an alpha-hydroxy acid that has been thoroughly researched for potential applications in health products (e.g., photoaging, uneven pigmentation, and antimicrobial qualities).

- In Wistar and Sprague-Dawley rats, mandelic acid undergoes one-directional chiral inversion (S-MA to R-MA) in vivo.
- In a mouse model of pain (acetic acid-induced writhing test), oral administration of mandelic acid at doses of 140, 200, and 300 mg/kg once daily significantly reduced the number of writhes and prolonged the pain threshold compared to the blank control group (P < 0.01). The high-dose group (300 mg/kg) showed fewer writhes than the aspirin positive control group. In the hot plate test, all mandelic acid dose groups showed higher pain threshold improvement rates than the positive control group, with the high-dose group showing a statistically significant difference (P < 0.05). However, in the xylene-induced ear edema test, mandelic acid did not show significant anti-inflammatory effects compared to the control group (P > 0.05).
- After oral administration of a single dose of 100 mg/kg (S)-mandelic acid to Sprague-Dawley rats, the compound undergoes metabolic conversion in vivo to generate (R)-glycolic acid.
- In a rabbit vaginal irritation test, mandelic acid-containing gel formulations at concentrations of 10, 20, and 40 mg/mL produced vaginal irritation scores of 1.69 ± 1.04, 2.98 ± 0.77, and 4.35 ± 1.04, respectively, all within the clinically acceptable range (<8). The vehicle control scored 1.38 ± 0.65, while the nonoxynol-9 gel control scored 7.88 ± 1.67 (P < 0.01). Mandelic acid exposure did not exert obvious effects on the integrity of spermatozoa membrane structures and only caused slight irritation to the rabbit vaginal epithelium.

- FRET-based sortase A inhibition assay: The inhibitory effect of mandelic acid on S. aureus sortase A (SrtA) was studied using a fluorescence resonance energy transfer (FRET) assay. A fluorescence-labeled peptide substrate (Abz-LPETG-Dap(Dnp)-NH₂) was used, where SrtA cleaves the peptide bond between T and G, resulting in increased fluorescence intensity due to the separation of the fluorophore (Abz) from the quencher (Dnp). Mandelic acid was incubated with SrtA and the substrate in reaction buffer. The IC50 value was calculated based on the concentration-dependent inhibition of fluorescence increase. The IC50 of mandelic acid against SrtA was determined to be 66.15 ± 24.39 μg/mL. Molecular docking and molecular dynamics simulations were further employed to elucidate the binding mechanism, showing that mandelic acid binds tightly to the active center of SrtA via various intermolecular forces, causing conformational changes that reduce enzyme activity.
- Aldo-keto reductase binding assay: The affinity of (S)-mandelic acid for aldo-keto reductase family 1 member B1 (AKR1B1) was evaluated using standard enzyme inhibition assays. The compound exhibited affinity activity with a Ki value of 100 μM, indicating competitive inhibition of the enzyme.

- Sperm immobilization assay: Human sperm samples were collected and prepared. Sperm motility was assessed by computer-aided sperm analysis (CASA). Various concentrations of mandelic acid were added to the sperm suspensions. Sperm immobilization was observed, and the minimum effective concentration (0.86 mg/mL) and median effective concentration (0.54 mg/mL) for inducing immobilization within 20 seconds were determined. Plasma membrane integrity was assessed using fluorescein isothiocyanate-pisum sativum agglutinin (FITC-PSA) staining, and mitochondrial membrane potential was assessed using JC-1 dye. Mandelic acid treatment caused mild plasma membrane injury but induced significant mitochondrial depolarization.
- Chiral inversion study in hepatocytes: Rat hepatocytes were isolated and cultured. S-Mandelic acid was added to the hepatocyte culture medium and incubated for 2 hours. Following incubation, the culture medium was analyzed for the presence of R-mandelic acid. The results showed that S-mandelic acid underwent chiral inversion to R-mandelic acid in rat hepatocytes. Control experiments using acidic and neutral phosphate buffers, HepG2 cells, and intestinal flora showed no conversion of mandelic acid enantiomers, indicating that the inversion is mediated by hepatic metabolic enzymes.

- Analgesic and anti-inflammatory study in mice: Fifty Kunming specific pathogen-free (SPF) mice were randomly divided into 5 groups: blank control group (normal saline, 0.1 mL/10 g), mandelic acid high-dose (300 mg/kg), medium-dose (200 mg/kg), low-dose (140 mg/kg) groups, and an aspirin positive control group. All treatments were administered orally once daily. The analgesic effect was evaluated using the acetic acid-induced writhing test and the hot plate test. For the writhing test, mice received intraperitoneal injection of acetic acid and the number of writhes was counted. For the hot plate test, the latency of paw licking or jumping was measured before and after treatment. The anti-inflammatory effect was evaluated using the xylene-induced ear edema model: xylene was applied to the ear, and after treatment, ear punch weights were measured to assess edema. Results showed that all mandelic acid doses significantly reduced writhing times and prolonged pain threshold (P < 0.01 vs. control), with the high-dose group showing fewer writhes than the aspirin group (P > 0.05). However, no significant anti-inflammatory effect was observed in the ear edema model (P > 0.05).
- Single-dose oral administration in rats: Sprague-Dawley rats received a single oral dose of 100 mg/kg (S)-mandelic acid. Following administration, the metabolic conversion of (S)-mandelic acid to (R)-glycolic acid was monitored in vivo.
- Rabbit vaginal irritation test: A mandelic acid-containing gel formulation was prepared at concentrations of 10, 20, and 40 mg/mL. The gel was administered intravaginally to rabbits. Local tolerance was evaluated by histopathological examination of vaginal tissue. The vaginal irritation scores were calculated based on a scoring system. The scores for the mandelic acid gel groups were 1.69 ± 1.04 (10 mg/mL), 2.98 ± 0.77 (20 mg/mL), and 4.35 ± 1.04 (40 mg/mL), all within the clinically acceptable range (<8). The vehicle control scored 1.38 ± 0.65, and the nonoxynol-9 gel control scored 7.88 ± 1.67 (P < 0.01). Mandelic acid only caused slight irritation to the rabbit vaginal epithelium.

- Chiral inversion metabolism: Mandelic acid undergoes one-directional chiral inversion (S-mandelic acid to R-mandelic acid) in rats in vivo. In vitro studies showed that S-mandelic acid is converted to R-mandelic acid in rat hepatocytes, whereas the enantiomers remain unchanged in acidic and neutral phosphate buffers, HepG2 cells, and intestinal flora. The synthetic S-MA-CoA thioester is rapidly racemized and hydrolyzed to R-MA by rat liver homogenate and subcellular fractions (S9, cytosolic, and mitochondrial fractions). This suggests that the chiral inversion mechanism involves the hydrolysis of S-MA-CoA and is similar to that of 2-arylpropionic acid (2-APA) drugs.
- Renal excretion: Studies in dogs using carbon-11-labeled mandelic acids showed progressive renal excretion with accumulation of radioactivity in the bladder and eventual excretion by the kidneys.

- Chiral inversion metabolism: Mandelic acid undergoes one-directional chiral inversion (S-mandelic acid to R-mandelic acid) in rats in vivo. In vitro studies showed that S-mandelic acid is converted to R-mandelic acid in rat hepatocytes, whereas the enantiomers remain unchanged in acidic and neutral phosphate buffers, HepG2 cells, and intestinal flora. The synthetic S-MA-CoA thioester is rapidly racemized and hydrolyzed to R-MA by rat liver homogenate and subcellular fractions (S9, cytosolic, and mitochondrial fractions). This suggests that the chiral inversion mechanism involves the hydrolysis of S-MA-CoA and is similar to that of 2-arylpropionic acid (2-APA) drugs.
- Renal excretion: Studies in dogs using carbon-11-labeled mandelic acids showed progressive renal excretion with accumulation of radioactivity in the bladder and eventual excretion by the kidneys.

[1]. dl-Mandelic acid exhibits high sperm-immobilizing activity and low vaginal irritation: A potential non-surfactant spermicide for contraception. Biomed Pharmacother. 2020;126:110104.

[2]. DL-mandelic acid intercalated Zn-Al layered double hydroxide: A novel antimicrobial layered material. Colloids Surf B Biointerfaces. 2018;165:111-117.

- Mandelic acid has been historically used as a urinary tract antiseptic and oral antibiotic, often in combination with methenamine (as methenamine mandelate). Currently, it is rarely used in systemic therapy and is instead primarily utilized in dermatology as a chemical peel due to its exfoliating properties, particularly for photoaging, irregular pigmentation, and acne.
- In cosmetic applications, mandelic acid is a slow-acting chemical peel suitable for all skin types, including sensitive and rosacea-prone skin, as well as skin of color. It is a lipophilic acid that penetrates the skin slowly and uniformly, making it an ideal peel for sensitive or aging and thin skin types.
- The (R)-isomer of mandelic acid is used in the synthesis of cephalosporins, penicillins, anticancer agents, and anti-obesity drugs, while the (S)-isomer is used in the preparation of nonsteroidal anti-inflammatory drugs such as deracoxib and celecoxib.
- Mandelic acid is used as a biological indicator of occupational exposure to styrene, a hazardous environmental pollutant classified as a human carcinogen. In unexposed populations, endogenous mandelic acid levels are up to 5 mg/L. Occupational exposure guidelines recommend a Biological Exposure Index (BEI) of 800 mg/g creatinine (end of shift), with decrements in psychomotor performance observed at urine levels >1200 mg/L.

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Mandelic acid is a 2-hydroxy monocarboxylic acid formed by replacing the two methyl hydrogen atoms in an acetic acid molecule with phenyl and hydroxyl groups. It possesses antibacterial activity and is a byproduct of human xenobiotic metabolism. Mandelic acid is a 2-hydroxy monocarboxylic acid belonging to the benzene family. It is functionally related to acetic acid and is the conjugate acid of mandelate. Mandelic acid is an approved aromatic α-hydroxy acid. It can be used as an ingredient in cosmetics and topical medications. Mandelic acid has been reported to exist in dye bezoar (Pisolithus tinctorius), root bezoar (Pisolithus arhizus), and other organisms with relevant data. Mandelic acid is an aromatic α-hydroxy acid used to treat urinary tract infections and can also be used as an oral antibiotic. See also: Ammonium mandelate (note moved to).

C8H8O3

152.1473

152.047

90-64-2

Mandelic acid-2,3,4,5,6-d5;70838-71-0

1292

White to off-white solid powder

1.3±0.1 g/cm3

321.8±22.0 °C at 760 mmHg

119-121ºC(lit.)

162.6±18.8 °C

0.0±0.7 mmHg at 25°C

1.591

0.92

2

3

2

11

138

0

C1=CC=C(C=C1)C(C(=O)O)O

IWYDHOAUDWTVEP-UHFFFAOYSA-N

InChI=1S/C8H8O3/c9-7(8(10)11)6-4-2-1-3-5-6/h1-5,7,9H,(H,10,11)

2-hydroxy-2-phenylacetic acid

MANDELIC ACID; dl-Mandelic acid; (±)-Mandelic acid; DL-Mandelic acid; 2-hydroxy-2-phenylacetic acid; 90-64-2; Phenylglycolic acid;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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 (~657.25 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (16.43 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 (16.43 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 (16.43 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.)