Zaragozic Acid A (Synonyms: Squalestatin S1) |
Katalog-Nr.GC12351
One-Click Copy Product Info
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Zaragozic Acid A is a competitive inhibitor of squalene synthase, with a Ki value of 78pM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 142561-96-4
Sample solution is provided at 25 µL, 10mM.
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Zaragozic Acid A is a competitive inhibitor of squalene synthase, with a Ki value of 78pM [1]. Zaragozic Acid A inhibits hepatic cholesterol synthesis, with an IC50 value of 6μM[2]. Zaragozic Acid A impairs staphyloxanthin formation and is a potent biofilm inhibitor in S. aureus and Bacillus subtilis by targeting CrtM enzyme without causing cell death[3]. Zaragozic Acid A has been widely used to regulate the cholesterol levels within cells and to inhibit the transformation of bronchial fibroblasts into myofibroblasts[4].
In vitro, Zaragozic Acid A treatment (100μM) for 72 hours significantly reduced the cholesterol level and increased the dolichol (Dol)-P-Man levels in human primary skin fibroblasts (HPSFs) with congenital disorders of glycosylation (CDG)[5]. Treatment with 10μg/ml Zaragozic Acid A for 48 hours would impair the maintenance of the Tat2p protein and the absorption of tryptophan in the tryptophan auxotrophic (trp1) yeast cells[6]. Treatment with 10μM Zaragozic Acid A for 48 hours significantly inhibited the replication of live Dengue virus type 2 (DEN-2 NGC) in K562 cells, with an EC50 value of 8.3μM[7].
In vivo, Zaragozic acid A treatment (3mg/kg/day; s.c.) caused massive production of Farnesol-derived dicarboxylic acids in urine of female Swiss Webster mice [8].
References:
[1] Bergstrom J D, Kurtz M M, Rew D J, et al. Zaragozic acids: a family of fungal metabolites that are picomolar competitive inhibitors of squalene synthase[J]. Proceedings of the National Academy of Sciences, 1993, 90(1): 80-84.
[2] Ponpipom M M, Girotra N N, Bugianesi R L, et al. Structure-activity relationships of C1 and C6 side chains of zaragozic acid A derivatives[J]. Journal of medicinal chemistry, 1994, 37(23): 4031-4051.
[3] Liu C I, Jeng W Y, Chang W J, et al. Binding modes of zaragozic acid A to human squalene synthase and staphylococcal dehydrosqualene synthase[J]. Journal of Biological Chemistry, 2012, 287(22): 18750-18757.
[4] Michalik M, Soczek E, Kosińska M, et al. Lovastatin-induced decrease of intracellular cholesterol level attenuates fibroblast-to-myofibroblast transition in bronchial fibroblasts derived from asthmatic patients[J]. European Journal of Pharmacology, 2013, 704(1-3): 23-32.
[5] Haeuptle M A, Welti M, Troxler H, et al. Improvement of dolichol-linked oligosaccharide biosynthesis by the squalene synthase inhibitor zaragozic acid[J]. Journal of Biological Chemistry, 2011, 286(8): 6085-6091.
[6] Daicho K, Maruyama H, Suzuki A, et al. The ergosterol biosynthesis inhibitor zaragozic acid promotes vacuolar degradation of the tryptophan permease Tat2p in yeast[J]. Biochimica et Biophysica Acta (BBA)-Biomembranes, 2007, 1768(7): 1681-1690.
[7] Rothwell C, LeBreton A, Ng C Y, et al. Cholesterol biosynthesis modulation regulates dengue viral replication[J]. Virology, 2009, 389(1-2): 8-19.
[8] Vaidya S, Bostedor R, Kurtz M M, et al. Massive production of farnesol-derived dicarboxylic acids in mice treated with the squalene synthase inhibitor zaragozic acid A[J]. Archives of biochemistry and biophysics, 1998, 355(1): 84-92.
| Cell experiment [1]: | |
Cell lines | Human primary skin fibroblasts (HPSFs) |
Preparation Method | Approximately 4×107 HPSF cells were cultured in DMEM medium containing low glucose (5mM) for 72 hours, and 2% fetal bovine serum and 100μM Zaragozic Acid A or DMSO were added to the medium as negative controls. The cells were incubated in DMEM medium containing 0.5mM glucose and 125μCi [3H]Man for 30 minutes for labeling. Dol-P-Man and short-chain lipid-linked oligosaccharide (LLO) were extracted once with chloroform/methanol (2:1), and twice with chloroform/methanol (3:2). The organic phases were combined, dried, and washed. The silica gel 60 thin-layer chromatography method was used with chloroform/methanol/water (65:25:4) as the developing agent for separation. After enhancing the signal with spray, the chromatogram plate was analyzed by X-ray photography. The region containing Dol-P-Man was scraped and counted in a liquid scintillation counter. |
Reaction Conditions | 100μM; 72h |
Applications | Zaragozic Acid A treatment notably increased Dol-P-Man levels in HPSFs. |
| Animal experiment [2]: | |
Animal models | Female Swiss Webster mice |
Preparation Method | Female Swiss Webster mice weighing approximately 25g were divided into five groups, three mice per group, and housed in metabolic cages. Groups I and II were treated as controls. Group I was dosed subcutaneously with saline (50μl) and 30min later gavaged with 10μCi of R,S-[5-3H]mevalonolactone. Similar to group I, group II was administered saline subcutaneously and 30min later gavaged with 25μCi of R,S-[5-3H]mevalonolactone containing 375nmol of unlabeled R,S-mevalonolactone. Groups III and IV were dosed with Zaragozic acid A (3mg/kg/day) subcutaneously. Thirty minutes after the Zaragozic acid A treatment, group III was gavaged with 25μCi of R,S-[5-3H]mevalonolactone containing 375nmol of unlabeled R,S-mevalonolactone and group IV was gavaged with 10μCi of R,S-[5-3H]mevalonolactone alone. Group V was gavaged with 5μCi of [1-14C]farnesol containing 45μmol of unlabeled farnesol. Urine from each group was collected for 72h. The dicarboxylic acid fractions were extracted and analyzed by TLC as free acids or converted to methyl esters and characterized by C18 reverse-phase column using HPLC. |
Dosage form | 3mg/kg/day for 3 days; s.c. |
Applications | Zaragozic acid A treatment caused massive production of Farnesol-derived dicarboxylic acids in urine of mice. |
References: | |
| Cas No. | 142561-96-4 | SDF | |
| Überlieferungen | Squalestatin S1 | ||
| Chemical Name | (1S,3S,4S,5R,6R,7R)-1-((4S,5R)-4-acetoxy-5-methyl-3-methylene-6-phenylhexyl)-6-(((4S,6S,E)-4,6-dimethyloct-2-enoyl)oxy)-4,7-dihydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid | ||
| Canonical SMILES | O[C@@H]1[C@H]([C@@]2([C@](C(O)=O)([C@H](O[C@@]1(CCC([C@H]([C@@H](CC3=CC=CC=C3)C)OC(C)=O)=C)O2)C(O)=O)O)C(O)=O)OC(/C=C/[C@H](C[C@H](CC)C)C)=O | ||
| Formula | C35H46O14 | M.Wt | 690.73 |
| Löslichkeit | H2O : 1 mg/mL (1.45 mM; Need ultrasonic and warming) | Storage | Store at -20°C,protect from light |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.4477 mL | 7.2387 mL | 14.4774 mL |
| 5 mM | 289.5 μL | 1.4477 mL | 2.8955 mL |
| 10 mM | 144.8 μL | 723.9 μL | 1.4477 mL |
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Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
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Average Rating: 5 (Based on Reviews and 17 reference(s) in Google Scholar.)