CAS 500-38-9 Nordihydroguaiaretic Acid - Analytical Products / Alfa Chemistry

CAT	APS500389
CAS	500-38-9
Structure
MDL Number	MFCD00002206
Synonyms	Butane, 1,4-bis(3,4-dihydroxyphenyl)-2,3-dimethyl-, 4-[4-(3,4-Dihydroxyphenyl)-2,3-dimethylbutyl]benzene-1,2-diol, Dinorguaiaretic acid, dihydro-, 4,4'-(2,3-Dimethyl-1,4-butanediyl)bis[1,2-benzenediol], β,γ-Dimethyl-α,δ-bis(3,4-dihydroxyphenyl)butane, NDGA, Dihydronorguaiaretic acid, 1,4-Bis(3,4-dihydroxyphenyl)-2,3-dimethylbutane,1,2-Benzenediol, 4,4'-(2,3-dimethyl-1,4-butanediyl)bis-, Pyrocatechol, 4,4'-(2,3-dimethyltetramethylene)di- (8CI), 4,4'-(2,3-Dimethyltetramethylene)dipyrocatechol, Nordihydroguaiaretic acid, NSC 4291, Norguaiaretic acid, dihydro-, 4,4'-(2,3-Dimethyl-1,4-butanediyl)bis(pyrocatechol)
IUPAC Name	4-[4-(3,4-dihydroxyphenyl)-2,3-dimethylbutyl]benzene-1,2-diol
Molecular Weight	302.36
Molecular Formula	C18H22O4
EC Number	207-903-0
Canonical SMILES	CC(Cc1ccc(O)c(O)c1)C(C)Cc2ccc(O)c(O)c2
InChI	InChI=1S/C18H22O4/c1-11(7-13-3-5-15(19)17(21)9-13)12(2)8-14-4-6-16(20)18(22)10-14/h3-6,9-12,19-22H,7-8H2,1-2H3
InChI Key	HCZKYJDFEPMADG-UHFFFAOYSA-N
REAXYS Number	2056826

Description	≥90% (HPLC), from Larrea divaricata (creosote bush)
Accurate Mass	302.1518
Assay	≥90% (HPLC)
Format	Neat
Linear Formula	[-CH(CH3)CH2C6H3-1,2-(OH)2]2
MP	184-186 °C (lit.)
Size	500MG, 1G, 5G
Storage Conditions	+20°C
Subcategory	Food additives, flavours and adulterants

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Case Study

Nordihydroguaiaretic Acid for Ferroptosis Inhibition in Nucleus Pulposus Cells and the Treatment of Intervertebral Disc Degeneration

Zhang, Yekai, et al. International Immunopharmacology 143 (2024): 113590.

Nordihydroguaiaretic acid (NDGA), a naturally occurring lignan, has emerged as a potent inhibitor of ferroptosis in the context of intervertebral disc degeneration (IVDD), a major cause of low back pain and disability. This study identified NDGA as the most effective agent among a screened library of natural products in suppressing RSL3-induced ferroptosis in nucleus pulposus cells (NPCs), the primary cell type involved in disc homeostasis.
Mechanistic investigation revealed that NDGA enhances the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key transcriptional regulator of antioxidant responses. This activation leads to the upregulation of glutathione peroxidase 4 (GPX4), a central enzyme in ferroptosis suppression, thereby mitigating oxidative stress-induced lipid peroxidation and cellular death in NPCs. Additionally, NDGA was shown to inhibit extracellular matrix degradation and inflammatory responses, both critical factors in IVDD progression.
In vivo validation using a rat puncture-induced IVDD model demonstrated that intraperitoneal administration of NDGA significantly delayed disc degeneration, supporting its therapeutic potential. These findings underscore the utility of NDGA in modulating ferroptosis pathways and highlight its promise as a candidate for pharmacological intervention in degenerative disc disease.
In conclusion, Nordihydroguaiaretic acid is used for the inhibition of ferroptosis in nucleus pulposus cells and the treatment of intervertebral disc degeneration, offering a novel strategy for IVDD management through redox and transcriptional regulation.

Nordihydroguaiaretic Acid Used for the Inhibition of Protein Glycation and Preservation of Albumin Structure

Awasthi, Saurabh, R. Preethy, and N. T. Saraswathi. International journal of biological macromolecules 122 (2019): 479-484.

Nordihydroguaiaretic acid (NDGA), a lignan derived from Larrea tridentata, exhibits strong antiglycation activity and offers protective effects on protein structure, particularly serum albumin. Glycation-induced modifications, especially the formation of advanced glycation end products (AGEs), are implicated in the pathophysiology of aging and various chronic diseases. This study demonstrated that NDGA significantly inhibits AGE formation through molecular binding interactions with albumin, as confirmed by spectroscopic and circular dichroism (CD) analyses.
Thioflavin T fluorescence and confocal imaging showed that NDGA prevented glycation-induced aggregation of albumin, while CD spectra revealed that NDGA preserved the native α-helical conformation of bovine serum albumin (BSA), counteracting the β-sheet-rich structure characteristic of glycated proteins. Structural modeling indicated that NDGA protects key lysine residues (e.g., Lys20, Lys41, Lys131, Lys132) from glycation-mediated modifications, maintaining albumin's biological functions such as ligand binding and molecular transport.
At a concentration of 500 μM, NDGA retained approximately 40% of the α-helical content in glycated albumin, compared to a dramatic structural shift toward β-sheets in untreated samples. This structural preservation is critical, as glycation-induced conformational changes are known to impair albumin function and contribute to cytotoxic effects in red blood cells.
In summary, Nordihydroguaiaretic acid is used for the inhibition of protein glycation and the preservation of albumin structural integrity, making it a promising candidate for therapeutic applications in metabolic and degenerative disorders.

Nordihydroguaiaretic Acid Used for Delaying Neurodegeneration in Alzheimer's Disease Models

Siddique, Yasir Hasan, and Fahad Ali. Chemico-Biological Interactions 269 (2017): 59-66.

Nordihydroguaiaretic acid (NDGA), a phenolic lignan from Larrea tridentata, has demonstrated promising neuroprotective activity in an Alzheimer's disease (AD) transgenic Drosophila model. This study assessed NDGA's therapeutic potential by evaluating motor function, oxidative stress markers, and longevity following 30-day exposure at concentrations ranging from 20-80 μM.
NDGA treatment led to a dose-dependent improvement in climbing ability, a behavioral marker of neurodegeneration in flies expressing human Aβ-42 peptide. At 80 μM, NDGA delayed locomotor decline by 2.52-fold compared to untreated AD flies, comparable to the effect of the standard AD drug donepezil. Furthermore, NDGA exposure extended the lifespan of AD flies significantly, mirroring previous findings in mammalian models.
Biochemically, NDGA restored glutathione (GSH) levels, which were markedly depleted in AD flies, achieving up to a 2.62-fold increase at the highest dose. Concurrently, it suppressed elevated glutathione S-transferase (GST) activity, a stress-responsive enzyme upregulated in AD pathology, reducing it by up to 4.19-fold. These antioxidant effects are consistent with NDGA's reported efficacy in other oxidative stress-related diseases, including skin cancer.
In conclusion, Nordihydroguaiaretic acid is used for delaying neurodegeneration and modulating oxidative stress in Alzheimer's disease models, underscoring its therapeutic potential as a natural compound for age-related neurodegenerative conditions.