Anethole trithione Chemical Properties

Melting point:

111°

Boiling point:

353.09°C (rough estimate)

Density 

1.4406 (rough estimate)

refractive index 

1.5080 (estimate)

storage temp. 

2-8°C

solubility 

soluble in Chloroform

form 

powder to crystal

color 

Orange-colored prisms from butyl acetate

Odor

very bitter taste

InChI

InChI=1S/C10H8OS3/c1-11-8-4-2-7(3-5-8)9-6-10(12)14-13-9/h2-6H,1H3

InChIKey

KYLIZBIRMBGUOP-UHFFFAOYSA-N

SMILES

S1C(C2=CC=C(OC)C=C2)=CC(=S)S1

CAS DataBase Reference

532-11-6(CAS DataBase Reference)

NIST Chemistry Reference

3H-1,2-Dithiole-3-thione, 5-(4-methoxyphenyl)-(532-11-6)

Safety Information

HS Code 

2934.99.3000

Toxicity

LD50 orl-mus: 3850 mg/kg NIIRDN 6,25,82

Anethole trithione Usage And Synthesis

Description

Anethole trithione, also known as bile vita, anetholtrithion or anise trisulfide, is a secretory choleretic drug, which can significantly enhance liver glutathione levels, significantly enhance glutamyl cysteine synthase, glutathione reductase and glutathione sulfur Transferase activity, reduce glutathione peroxidase activity, enhance liver cell viability, and increase bile secretion. Without increasing the burden on the liver, it can reduce liver portal pressure, eliminate liver congestion and other symptoms of hepatitis lesions, promote liver cell activation, and contribute to the improvement and recovery of liver function.

Originator

Sialor,Paladin Labs

Uses

Anethole trithione is a choleretic drug that can be effective in the treatment of dry mouth, including drug-induced xerostomia. Research suggests that Anethole trithione may exert its therapeutic effects by acting on the alpha-CGRP nerves in the salivary glands, which in turn promotes salivary secretion^[1-2].

Preparation

Anethole trithione can be obtained by the cyclization of anethole and sulfur. Add aniseed oil and dimethylformamide to the reaction tank, stir, and then add sulfur powder. Heat to 146–150 °C, and maintain the reaction for 1.5 hours. At the end of the reaction, cool to 80 °C, recover dimethylformamide under reduced pressure, then cool the reaction mixture to 66 °C. Add xylene and activated carbon, heat to 108 °C, and hold for half an hour before hot filtration. Cool the filtrate to 0 °C to crystallize, then filter and wash with water to obtain the crude product. After refining with xylene or butyl acetate, the final product of anethole trithione is obtained. The yield is 40%.

Definition

ChEBI: Anethole trithione is a bile secretion-stimulating drug that restores salivation and relieves the discomfort of dry mouth in chemotherapy-induced xerostomia. In addition, this agent has exhibited chemopreventive properties. The mechanism of action for the chemopreventive and xerostomia properties have not been fully elucidated.

Manufacturing Process

1 mol anethol (1-methoxy-4-propenyl-benzene) and 3 mol sulfur were heated in an open vessel to temperature 190°-200°C. H2S was removed at this temperature. On cooling the reaction mixture was getting solid. The solid product was recrystallizated from acetone or ethanol to give the orange-red needles of 5-(4-methoxyphenyl)-3H-1,2-dithiole-3-thione; MP 108.5°C.

Therapeutic Function

Salivation stimulant, Choleretic, Neuroprotective

Pharmacokinetics

Anethole trithione (ATT) appears to have a broad range of unique functions, from increasing salivary secretion to help treat xerostomia, to demonstrating an ability to inhibit carcinogenesis by increasing the activity of electrophile detoxification enzymes, and even being used as an adjunctive therapy for cholecystitis, gallstone, indigestion, and acute/chronic hepatitis and is marketed in certain countries like France, Germany, and China. Unfortunately, many of the specific mechanisms of action to these activities have yet to be formally elucidated, which means that while studies are ongoing, ATT itself is not necessarily formally indicated for many of these aforementioned functions at this time and is only used in limited regions around the world.

Safety Profile

Poison by intramuscular route.Moderately toxic by ingestion and intraperitoneal routes.Experimental reproductive effects. When heated todecomposition it emits toxic fumes of SOx.

References

[1] TOSHIAKI NAGANO; Masaharu T. Enhancement of salivary secretion and neuropeptide (substance P, α-calcitonin gene-related peptide) levels in saliva by chronic anethole trithione treatment[J]. Journal of Pharmacy and Pharmacology, 2010. DOI:10.1211/0022357011778098.
[2] GLENERT U. Effects of chronic anethole trithione and amitriptyline treatment on rat parotid gland signalling[J]. European Journal of Pharmacology: Molecular Pharmacology, 1992. DOI:10.1016/0922-4106(92)90081-6.
[3] GLENERT U. Acute effects of a possible sialogogue, anethole trithione, in rat parotid glands[J]. European Journal of Pharmacology: Molecular Pharmacology, 1991, 208 4: Pages 287-295. DOI:10.1016/0922-4106(91)90074-R.
[4] Ukai, Y., Taniguchi, N., Takeshita, K., et al. Chronic anethole trithione treatment enhances the salivary secretion and increases the muscarinic acetylcholine receptors in the rat submaxillary gland. Arch. Int. Pharmacodyn. Ther. 271(2), 206-212 (1984).
[5] Reddy, B.S., Rao, C.V., Rivenson, A., et al. Chemoprevention of colon carcinogenesis by organosulfur compounds. Cancer Res. 53(15), 3493-3498 (1993).
[6] Ansher, S.S., Dolan, P., and Bueding, E. Chemoprotective effects of two dithiolthiones and of butylhydroxyanisole against carbon tetrachloride and acetaminophen toxicity. Hepatology 3(6), 932-935 (1983).

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