2731-16-0

Basic information

• Product Name: Thiocolciran
• Synonyms: Thiocolciran;(S)-5,6,7,9-Tetrahydro-1,2,3-trimethoxy-10-methylthio-9-oxobenzo[a]heptalen-7-amine;(S)-7-Amino-6,7-dihydro-1,2,3-trimethoxy-10-(methylthio)benzo[a]heptalen-9(5H)-one;Corps R-261;N-Deacetylthiocolchicine;R-261;(7S)-7-amino-1,2,3-trimethoxy-10-(methylthio)-6,7-dihydro-5H-benzo[a]heptalen-9-one;(7S)-7-amino-1,2,3-trimethoxy-10-methylsulfanyl-6,7-dihydro-5H-benzo[a]heptalen-9-one
• CAS NO: 2731-16-0
• Molecular Formula: C₂₀H₂₃NO₄S
• Molecular Weight: 373.471
• Mol File: 2731-16-0.mol
• Article Data: 16

Chemical Properties

• Melting Point: 198 °C
• Boiling Point: 631.6°Cat760mmHg
• Flash Point: 335.8°C
• Appearance: /
• Density: 1.1860 (rough estimate)
• Vapor Pressure: 7.33E-16mmHg at 25°C
• Refractive Index: 1.5800 (estimate)
• PKA: 8.62±0.40(Predicted)
• CAS DataBase Reference: Thiocolciran(CAS DataBase Reference)
• NIST Chemistry Reference: Thiocolciran(2731-16-0)
• EPA Substance Registry System: Thiocolciran(2731-16-0)

Safety Data

• Hazardous Substances Data: 2731-16-0(Hazardous Substances Data)

Usage

General Description

Thiocolchicoside is a chemical compound with muscle relaxant properties. It is derived from the natural plant alkaloid colchicine and is used to treat conditions such as muscle spasms and stiffness. Thiocolchicoside works by inhibiting the release of neurotransmitters involved in muscle contractions and has been shown to have anti-inflammatory and analgesic effects. It is commonly used as a topical gel or as an oral medication, and is generally well-tolerated with few side effects. Thiocolchicoside is also being studied for its potential in treating conditions such as chronic pain and fibromyalgia.

InChI:InChI=1/C20H23NO4S/c1-23-16-9-11-5-7-14(21)13-10-15(22)17(26-4)8-6-12(13)18(11)20(25-3)19(16)24-2/h6,8-10,14H,5,7,21H2,1-4H3/t14-/m0/s1

Upstream product

• 2730-71-4 thiocolchicine 
• 64-86-8 colchicine 
• 209810-39-9 thiocolchicine 
• 209810-38-8 N-(5,6,7,9-tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo[a]heptalen-7-yl) acetamide 
• 203584-67-2 (1S,4R)-4,7,7-Trimethyl-3-oxo-2-oxa-bicyclo[2.2.1]heptane-1-carboxylic acid ((S)-1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[a]heptalen-7-yl)-amide 
• 123643-53-8 (-)-N-5,6,7,10-tetrahydro-1,2,3-trimethoxy-10-thiomethyl-9-thiobenzoheptalene-7-yl-(S)-acetamide 

Downstream Products

• 63620-51-9 N-(ethoxycarbonyl)deacetylthiocolchicine 
• 147950-73-0 N-(4'-chlorobenzoyl)deacetylthiocolchicine 
• 2730-71-4 thiocolchicine 
• 103591-54-4 N-(3',4',5'-trimethoxybenzoyl)deacetylthiocolchicine 
• 147950-72-9 N-(4'-nitrobenzoyl)deacetylthiocolchicine 
• 147950-71-8 N-(3'-nitrobenzoyl)deacetylthiocolchicine 
• 76129-16-3 N-<5,6,7,9-tetrahydro-1,2,3-trimethoxy-9-oxo-10-(methylthio)-9-oxobenzoheptalen-7-yl>-(S)-2,2,2-trifluoroacetamide 
• 96737-27-8 N-(phenoxycarbonyl)deacetylthiocolchicine 

Relevant articles and documents

Stereochemical variations on the colchicine motif. Part 2.1 Unexpected tetracyclic isoxazole derivatives

Attempts to expand the colchicine B-ring in 7-oxodeacetamidothiocolchicine 1 by a Beckmann-type rearrangement lead to unexpected tetracyclic isoxazole derivatives 2 and 3. The syntheses, crystal and solution structures, conformational interconversions and binding properties to tubulin are reported. The molecules exist as mixtures of two enantiomeric conformations due to hindered rotation around the A and C rings, which are twisted by dihedral angles of 62° (1) and 46° (2) in the crystal. Solid, solution and gas phase (according to MM2) structures are compared. Dynamic 1H NMR analyses give the following thermodynamic parameters for the rotation around the A-C pivot bond: (1) ΔG?381 K = 77.4; (2) ΔG?300 K = 60.7; ΔH? = 55.6 ± 1.6 kJ mol-1; ΔS? = -16.7 ± 15 J mol-1 K-1; (3) ΔG?298 K = 60.1, ΔH? = 59.9 ± 2.0 J mol-1 and ΔS? = -0.7 ± 15 J mol-1 K-1. The drugs 1 and 2 depolymerize microtubules by binding to tubulin according to both in vitro and in vivo studies, but 1 is considerably more active than 2. Compound 3 does not seem to bind notably to tubulin.

Synthesis, anticancer activity and molecular docking studies of N-deacetylthiocolchicine and 4-iodo-N-deacetylthiocolchicine derivatives

Colchicine is a plant alkaloid with a broad spectrum of biological and pharmacological properties. It has found application as an anti-inflammatory agent and also shows anticancer effects through its ability to destabilize microtubules by preventing tubulin dimers from polymerizing leading to mitotic death. However, adverse side effects have so far restricted its use in cancer therapy. This has led to renewed efforts to identify less toxic derivatives. In this article, we describe the synthesis of a set of novel double- and triple-modified colchicine derivatives. These derivatives were tested against primary acute lymphoblastic leukemia (ALL-5) cells and several established cancer cell lines including A549, MCF-7, LoVo and LoVo/DX. The novel derivatives were active in the low nanomolar range, with 7-deacetyl-10-thiocolchicine analogues more potent towards ALL-5 cells while 4-iodo-7-deacetyl-10-thiocolchicine analogues slightly more effective towards the LoVo cell line. Moreover, most of the synthesized compounds showed a favorable selectivity index (SI), particularly for ALL-5 and LoVo cell lines. Cell cycle analysis of the most potent molecules on ALL-5 and MCF-7 cell lines revealed contrasting effects, where M-phase arrest was observed in MCF-7 cells but not in ALL-5 cells. Molecular docking studies of all derivatives to the colchicine-binding site were performed and it was found that five of the derivatives showed strong β-tubulin binding energies, lower than ?8.70 kcal/mol, while the binding energy calculated for colchicine is ?8.09 kcal/mol. The present results indicate that 7-deacetyl-10-thiocolchicine and 4-iodo-7-deacetyl-10-thiocolchicine analogues constitute promising lead compounds as chemotherapy agents against several types of cancer.

7-Deacetyl-10-alkylthiocolchicine derivatives-new compounds with potent anticancer and fungicidal activity

A series of new semi-synthetic 7-deacetyl-10-alkylthiocolchicne derivatives with ethyl, n-propyl, i-propyl and n-butyl substituents were synthesised and characterised by spectroscopic methods, elemental analysis, DFT calculations and molecular docking simulations. All the synthesized compounds have been tested for fungicidal and anticancer activities against SKOV-3, LoVo, MCF-7, MDA-MB-231 and the lung-derived fibroblast CCD39Lu. All the new colchicine derivatives exhibit significantly higher cytotoxicity towards the SKOV-3 tumour cell line than the natural product-colchicine. The most effective cytotoxic agents were 7-deacetyl-10-n-buthylthiocolchicine and 7-deacetyl-10-i-propylthiocolchicine. Among all the compounds tested, 7-deacetyl-10-n-buthylthiocolchicine exhibited the highest fungicidal activity. Molecular modeling indicated that several mutations found in the β-tubulin unit of the tested fungal strains are crucial for antifungal activity and selectivity of 7-deacetyl-10-n-buthylthiocolchicine. The obtained results may be useful for the development of selective colchicine derivatives as effective fungicidal and/or anticancer drugs.