Microtubule; tubulin polymerization

Thiocolchicine has IC50 values of 0.01 μM, 0.021 μM, 0.398 μM, 0.011 μM, and 0.114 μM for MCF-7, LoVo, LoVo/DX, A-549, and BALB/3T3 cells, respectively [3]. Thiocolchicine (1 nM-100 μM; 24-72 hours) exhibits a correlation between growth suppression and cell cycle blocking activities in breast cancer cells. It suppresses the growth of MDR CEM-VBL leukemia cells (IC50=50 nM) and multidrug-resistant (MDR) MCF-7 ADRr breast cancer cells (IC50=0.6 nM and 400 nM, respectively) [2].

mouse LD50 intraperitoneal 997 ug/kg Journal of Medicinal Chemistry., 24(636), 1981

[1]. Structural requirements for the binding of colchicine analogs to tubulin: the role of the C-10 substituent. Bioorganic & Medicinal Chemistry Letters.Volume 1, Issue 9, 1991, Pages 471-476.

[2]. Antiproliferative Activity of Colchicine Analogues on MDR-positive and MDR-negative Human Cancer Cell Lines. Anticancer Drug Des. 1998 Jan;13(1):19-33.

Thiocolchicine is an antimitotic alkaloid that binds to microtubules and inhibits tubulin polymerization and induces apoptosis. (NCI)

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Derivatives of colchicine and the bicyclic colchicine analog 2-methoxy-5-(2',3',4'-trimethoxyphenyl)tropone were tested for inhibition of tubulin polymerization. The nature of the tropone substituent had litte effect on the efficacy of the colchicine series, with some exceptions. In contrast, the potency of the bicyclic analogs varied greatly with the tropone substituent. Derivatives of colchicine (I) and its bicyclic analog (II) with varying tropone substituents (R) were prepared and assayed for inhibition of microtubule assembly. Significantly greater variations in potency are observed in the bicyclic series than in the colchicine series.[1]

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In this study the in vitro antitumor activity of a series of 20 colchicine analogues was tested and compared with colchicine and thiocolchicine on three different human cancer cell lines, two of which express the multidrug-resistance (MDR) phenotype. At concentrations from 1 nM to 100 microM, all compounds tested inhibited cancer cell proliferation. The IC50 values indicate that the three fluorinated analogues were the most active compounds, with a similar decreasing order of potency (IDN 5005 > IDN 5079 > IDN 5080) on the two MDR-expressing cell lines, whereas thiocolchicine was the most effective compound on the MDR-negative MDA-MB 231 cells. A strong correlation (r = 0.94; P = 0.004) was found between IC50 values obtained using the two MDR-positive cell lines. Conversely, IC50 values obtained in MDA-MB 231 cells did not show a significant correlation with MDR-positive cell lines, thereby suggesting some difference in the antiproliferative mechanism(s) of colchicine analogues. Cell cycle analysis of the most active analogues in breast cancer cells showed a relationship between cell cycle blocking activity and growth inhibition. The most active agents on the MDR-positive MCF7 ADRr cell line, after 24 h of culture, in terms of cell cycle blocking activity were the three fluorinated analogues. Interestingly, after 72 h, when the cell cycle block subsided, a consistent amount of DNA fragmentation was evident. The extent of cell cycle block, measured as the G2/G1 ratio, was significantly correlated with the apoptosis rate expressed as a percentage of DNA fragmentation on both cell lines, thereby suggesting that a large number of blocked cells underwent the apoptotic pathway.[2]

C22H25NO5S

415.5026

415.145

C, 63.59; H, 6.06; N, 3.37; O, 19.25; S, 7.72

2730-71-4

Thiocolchicine-d3;1314417-95-2

17648

Light yellow to green yellow solid powder

1.27g/cm3

729.1ºC at 760mmHg

394.7ºC

4.12E-21mmHg at 25°C

1.609

3.975

1

6

5

29

744

1

CC(=O)N[C@H]1CCC2=CC(=C(C(=C2C3=CC=C(C(=O)C=C13)SC)OC)OC)OC

CMEGANPVAXDBPL-INIZCTEOSA-N

InChI=1S/C22H25NO5S/c1-12(24)23-16-8-6-13-10-18(26-2)21(27-3)22(28-4)20(13)14-7-9-19(29-5)17(25)11-15(14)16/h7,9-11,16H,6,8H2,1-5H3,(H,23,24)/t16-/m0/s1

N-[(7S)-1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]acetamide

Thiocolchicine; 2730-71-4; Thiocholchicine; Colchicine, 10-thio-; NSC 186301; Colchicine, 10-demethoxy-10-(methylthio)-; EINECS 220-346-8; 10-Demethoxy-10-methylthiocolchicine;

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)

DMSO : ~100 mg/mL (~240.67 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.02 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (6.02 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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