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].

The intraperitoneal LD50 in mice was 997 ug/kg. (Journal of Pharmaceutical 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, inhibiting tubulin polymerization and inducing apoptosis. (NCI)

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We tested the inhibitory effects of colchicine derivatives and their bicyclic analog 2-methoxy-5-(2',3',4'-trimethoxyphenyl)cycloheptatrienone on tubulin polymerization. With a few exceptions, the nature of the cycloheptatrienone substituent had little effect on the potency of the colchicine series compounds. In contrast, the potency of the bicyclic analog varied considerably with different cycloheptatrienone substituents. We prepared colchicine derivatives (I) and their bicyclic analogs (II) with different cycloheptatrienone substituents (R) and examined their inhibitory effects on microtubule assembly. The potency of the bicyclic series compounds varied significantly more than that of the colchicine series compounds. [1]

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This study tested the in vitro antitumor activity of 20 colchicine analogues and compared them with colchicine and thiocolchicine in three different human cancer cell lines, two of which expressed a multidrug resistance (MDR) phenotype. All tested compounds inhibited cancer cell proliferation in a concentration range of 1 nM to 100 μM. IC50 values showed that the three fluorinated analogues had the highest activity, with decreasing potency in the two MDR-expressing cell lines (IDN 5005 > IDN 5079 > IDN 5080), while thiocolchicine showed the highest activity in MDR-negative MDA-MB 231 cells. There was a significant correlation between the IC50 values obtained using the two MDR-positive cell lines (r = 0.94; P = 0.004). In contrast, no significant correlation was shown between the IC50 values obtained in MDA-MB 231 cells and the MDR-positive cell lines, suggesting that the antiproliferative mechanisms of colchicine analogues may differ. Cell cycle analysis of the most active analogs in breast cancer cells showed an association between cell cycle arrest activity and growth inhibition. After 24 hours of culture in MDR-positive MCF7 ADRr cell lines, the three fluorinated analogs were the most active in terms of cell cycle arrest activity. Interestingly, after 72 hours, persistent DNA fragmentation was observed when cell cycle arrest subsided. The degree of cell cycle arrest (measured by the G2/G1 ratio) was significantly correlated with the apoptosis rate expressed as the percentage of DNA fragmentation in both cell lines, indicating that a large number of arrested 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.)