4-Formylcolchicine   中文名称: 4-甲酰秋水仙碱

Microtubule/Tubulin

4-Formylcolchicine（化合物 7）对 A549、HT-29 和 HCT116 细胞具有抗增殖作用，IC50 分别为 1.007、0.128 和 0.054 µM[1]。

通过慢性（7周）给大鼠施用CCl4诱导肝纤维化。动物分为四组：（a）对照组，（b）单独用CCI治疗组，（c）用CCl4和秋水仙碱治疗组，以及（d）用CCl_4和与乳酰化血清白蛋白结合的4-Formylcolchicine/甲酰秋水仙素治疗组。通过生化检测（碱性磷酸酶[ALP]、γ-谷氨酰转移酶[γGT]、天冬氨酸和丙氨酸转氨酶[AST和ALT]、白蛋白和总胆红素）监测肝功能障碍。通过测定羟脯氨酸和显微镜检查来评估纤维化。接触CCl4会导致肝脏结构和胶原蛋白沉积发生重大变化。秋水仙碱部分抵消了这些影响，FC-LASA在更大程度上抵消了这些作用。形态学发现与生化数据相吻合。这里报告的信息表明，秋水仙碱对中毒大鼠的肝脏具有抗纤维化活性，FC-LASA作为抗纤维化药物比秋水仙碱本身更具活性[1]。

细胞活力测定[1]
细胞类型： A549、HT-29、HCT116 细胞
测试浓度： 0-5 µM
孵育时间： 24 小时
实验结果： 抑制细胞生长，对 A549、HT-29、HCT116 细胞的 IC50 值分别为 1.007、0.128、0.054 µM。

Effect of colchicine and its derivatives on liver fibrosis [1]
To study the effects of colchicine derivatives on liver fibrosis in vivo, we used adult Sprague-Dawley male rats (about 250 g body wt.). The animals were divided into four groups. (A) Controls received 2 ml.kg-1 body wt. mineral oil by intraperitoneal route and 250 ~tl of saline by injection into the tail vein three times a week for 7 weeks; (B) Animals were intoxicated with carbon tetrachloride. They were treated as those of groups A, except that they received a mixture of mineral oil and carbon tetrachloride (65:35 v/v, 2 ml'kg-1 body wt.); (C) The animals belonging to this group were treated as those of group B but they received colchicine (120 ~tg-kg-1 body wt., dissolved in saline) instead of saline; and (D) animals were treated as in (C), but colchicine was replaced by FC-LASA (120 ~tg.kg-~ body wt., as free colchicine). Doses were adjusted to body wt. and expressed as free colchicine. Owing to the high toxicity of CC14 (only about 40-50% of the animals survived 7 weeks' treatment), we began the experiment with 50 animals (various treatments) and 15 animals (controls), to have the final number of animals reported in Table 1. At the end of the experiment, animals were anaesthetised with diethyl ether and their blood was drained by heart puncture and collected in pre-heparinated vessels. Plasma was prepared by centrifugation at 1000 x g for 10 min and some biochemical parameters (alkaline phosphatase (ALP), aspartate and alanine transaminases (AST and ALT) y-glutamyl transferase (yGT), albumin and total bilirubin) were determined by commercial kits. Livers were used to verify collagen content (as hydroxyproline) and for histological examination.

[1]. Formylcolchicine bound to lactosaminated serum albumin is a more active antifibrotic agent than free colchicine. Clin Chim Acta . 1996 Oct 29;254(2):149-57.

[2]. Design, Synthesis, and Antitumor Activity of 4-Halocolchicines and Their Pro-drugs Activated by Cathepsin B. ACS Med Chem Lett. 2011 Mar 4;2(5):348-52.

Histological findings agree with the biochemical tests and especially with the determination of liver hydroxyproline, which assesses liver fibrosis better than microscopic evaluation. All tests indicate that FC-LASA is more effective than colchicine to decrease liver fibrosis following CC14 administration in the rat. [1]

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Novel colchicine derivatives possessing various substituents at the C4 position were prepared. Among them, 4-halo derivatives 3-6 were found to exhibit higher activity against cancer cell lines (A549, HT29, HCT116) as well as on mice transplanted with the HCT116 human colorectal carcinoma cell line than colchicine (1). Further, utilizing the 4-substituted colchicines, we prepared pro-drugs having a dipeptide side chain and demonstrated that these pro-drugs were activated by cathepsin B, an enzyme overexpressed in tumor cells, and exhibited selective toxicity to the tumor cells.[2]

C23H25NO7

427.45

427.163

2730-82-7

332237

Light yellow to yellow solid powder

1.29g/cm3

786.9ºC at 760mmHg

429.7ºC

9.93E-25mmHg at 25°C

1.589

3.075

100.16

1

7

6

31

815

1

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

JUWAUXATKRGHCK-KRWDZBQOSA-N

InChI=1S/C23H25NO7/c1-12(26)24-17-8-6-14-16(11-25)21(29-3)23(31-5)22(30-4)20(14)13-7-9-19(28-2)18(27)10-15(13)17/h7,9-11,17H,6,8H2,1-5H3,(H,24,26)/t17-/m0/s1

N-[(7S)-4-formyl-1,2,3,10-tetramethoxy-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]acetamide

4-Formylcolchicine; 2730-82-7; NSC328403; NSC-328403; CHEMBL155693; DTXSID30950024;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中（例如氮气保护），避免吸湿/受潮和光照。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: 160 mg/mL (374.31 mM)

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。