Hydrolysis product of Fumonisin B1

Fumonisin B1 (FB1) is the predominant member of a family of mycotoxins produced by Fusarium moniliforme (Sheldon) and related fungi. Certain foods also contain the aminopentol backbone (AP1) that is formed upon base hydrolysis of the ester-linked tricarballylic acids of FB1. Both FB1 and, to a lesser extent, AP1 inhibit ceramide synthase due to structural similarities between fumonisins (as 1-deoxy-analogs of sphinganine) and sphingoid bases. To explore these structure-function relationships further, erythro- and threo-2-amino, 3-hydroxy- (and 3, 5-dihydroxy-) octadecanes were prepared by highly stereoselective syntheses. All of these analogs inhibit the acylation of sphingoid bases by ceramide synthase, and are themselves acylated with Vmax/Km of 40-125 for the erythro-isomers (compared with approximately 250 for D-erythro-sphinganine) and 4-6 for the threo-isomers. Ceramide synthase also acylates AP1 (but not FB1, under the conditions tested) to N-palmitoyl-AP1 (PAP1) with a Vmax/Km of approximately 1. The toxicity of PAP1 was evaluated using HT29 cells, a human colonic cell line. PAP1 was at least 10 times more toxic than FB1 or AP1 and caused sphinganine accumulation as an inhibitor of ceramide synthase. These studies demonstrate that: the 1-hydroxyl group is not required for sphingoid bases to be acylated; both erythro- and threo-isomers are acylated with the highest apparent Vmax/Km for the erythro-analogs; and AP1 is acylated to PAP1, a new category of ceramide synthase inhibitor as well as a toxic metabolite that may play a role in the diseases caused by fumonisins [2].

[1]. Effects of aminopentol on in utero development in rats. Food Chem Toxicol. 2006 Feb;44(2):161-9.

[2]. Acylation of naturally occurring and synthetic 1-deoxysphinganines by ceramide synthase. Formation of N-palmitoyl-aminopentol produces a toxic metabolite of hydrolyzed fumonisin, AP1, and a new category of ceramide synthase inhibitor. J B.

[3]. Induction of apoptosis by fumonisin B1 in HT29 cells is mediated by the accumulation of endogenous free sphingoid bases. Toxicol Appl Pharmacol. 1998 Feb;148(2):252-60.

(2S,3S,5R,10R,12S,14S,15R,16R)-2-amino-12,16-dimethyleicosano-3,5,10,14,15-pentanol is a pentanol with a structure similar to (3S,5R,10R,12S,14S,15R,16R)-12,16-dimethyleicosano-3,5,10,14,15-pentanol, except that the pro-S hydrogen at the 2-position is replaced by an amino group. It is a product of the hydrolysis of the O-acyl bond of fumonisin B1. It is a pentanol and also a primary amino compound. It is the conjugate base of (2S,3S,5R,10R,12S,14S,15R,16R)-2-amino-12,16-dimethyleicosano-3,5,10,14,15-pentanol (1+). Aminopentanol (AP1) is the backbone and major hydrolysis product of the fungal toxin fumonisin B1 (FB1), found in corn-based foods, which are an important part of the daily diet in some parts of the world. FB1 toxicity is thought to be related to altered sphingolipid metabolism, but the toxicity of AP1 is unclear. Epidemiological correlation and in vitro studies suggest that AP1 may increase the risk of neural tube defects (NTDs), but prior to this study, no in vivo developmental studies of AP1 had been conducted. Rats were administered AP1 once daily by gavage at doses of 0, 15, 30, 60, or 120 mg/kg during gestational days 3–16 (GD 3–16). Reproductive and developmental parameters were measured at GD 17 (one day after the last administration) and GD 20. Furthermore, sphingolipid content in maternal and fetal tissues was analyzed at GD 17. Conclusion: AP1 reduced maternal weight gain, but its toxicity was lower than that of FB1. AP1 is not teratogenic, does not affect tissue sphingolipid ratios, does not alter reproduction or fetal development, and has not produced dose-related histopathological effects in maternal mice. [1]

---

Zearalenone B1 (FB1) and aminopentanol (AP1) (formed by the hydrolysis of FB1) are present in maize contaminated with certain strains of Zearalenone. HT29 cells (a human colon cancer cell line) showed a significant reduction in cell number after incubation with either FB1 or AP1; AP1 was less potent, with 50 μM AP1 causing a reduction in cell number (approximately 30% after 24 hours) comparable to 10 μM FB1. The reduction in cell number reflected an increase in DNA fragmentation and the proportion of apoptotic cells. Both FB1 and AP1 led to the accumulation of sphingosine (10 μM FB1 and 50 μM AP1 resulted in 25-fold and 35-fold increases in sphingosine, respectively); therefore, FB1 and AP1 concentrations that resulted in comparable reductions in cell number also showed similar increases in sphingosine (a compound with growth-inhibiting and cytotoxic properties). The first step of inhibiting sphingolipid biosynthesis using ISP-1 can prevent FB1-induced increases in sphingosine, DNA fragmentation, and apoptosis. Therefore, these effects of FB1 on HT29 cells can be attributed to the accumulation of sphingosine. Since consuming food contaminated with Fusarium moniliforme (Sheldon) exposes colon cells to these mycotoxins, the toxicity of FB1 and AP1 to intestinal cells in vivo should be evaluated, especially in a recent report (Bhat et al., Clin. Toxicol. 35, 249, 1997) describing intestinal disturbances in humans after consuming moldy corn and sorghum containing fumonisins. [3]

C22H47NO5

405.61228

405.345

145040-09-1

21119850

Typically exists as solid at room temperature

1.051±0.06 g/cm3(Predicted)

593.8±50.0 °C(Predicted)

1.42E-16mmHg at 25°C

3.031

6

6

17

28

371

8

CCCC[C@@H]([C@@H]([C@@H](C[C@@H](C[C@H](CCCC[C@H](C[C@@H]([C@@H](N)C)O)O)O)C)O)O)C

UWWVLQOLROBFTD-GADKELDLSA-N

InChI=1S/C22H47NO5/c1-5-6-9-16(3)22(28)21(27)13-15(2)12-18(24)10-7-8-11-19(25)14-20(26)17(4)23/h15-22,24-28H,5-14,23H2,1-4H3/t15-,16+,17-,18+,19+,20-,21-,22+/m0/s1

(2S,3S,5R,10R,12S,14S,15R,16R)-2-amino-12,16-dimethylicosane-3,5,10,14,15-pentol

AP1 Metabolite; Aminopentol; Aminopentol formate salt; 145040-09-1; (2S,3S,5R,10S,12R,14R,15S,16S)-2-amino-12,16-dimethylicosane-3,5,10,14,15-pentol; 3,5,10,14,15-Eicosanepentol, 2-amino-12,16-dimethyl-, (2S,3S,5R,10R,12S,14S,15R,16R)-; 3,5,10,14,15-Eicosanepentol, 2-amino-12,16-dimethyl-, (2S-(2R*,3R*,5S*,10S*,12R*,14R*,15S*,16S*))-; 2-amino-12,16-dimethylicosane-3,5,10,14,15-pentol;

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

---

Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

View More

Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

---

Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

View More

Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

---

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

---

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