N-Desethyl amodiaquine
(Synonyms: 去乙基阿莫地喹) 目录号 : GC36709
N-Desethyl amodiaquine是一种抗寄生虫药物，对疟原虫菌株V1/S和3D7具有抑制作用，其IC50值分别为97nM和25nM。
Cas No.:79352-78-6
Sample solution is provided at 25 µL, 10mM.
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N-Desethyl amodiaquine is an antiparasitic agent, has inhibitory for strains V1/S and 3D7 with IC50 values of 97nM and 25nM, respectively[1]. N-Desethyl amodiaquine is the major metabolite of the antimalarial compound aminodiaquine, produced by the action of cytochrome P450 isoform 2C8[2]. N-Desethyl amodiaquine is highly active against Plasmodium falciparum and can synergize with amodiaquine, usually used in the research of malaria[3-4].
In vitro, treatment with N-Desethyl amodiaquine significantly blocked viral replication in both Huh 7 and Vero E6 cell lines infected with Ebola virus, with IC50 values of 2.8μM and 11μM[5]. Treatment of RAW264.7 cells with N-Desethyl amodiaquine (8, 16, 33, or 66μM) for 1h before 6h intoxication with 500ng/mL protective antigen (PA)+ 500ng/mL lethal factor (LF) inhibited proteinase B activity in a dose-dependent manner and reduced toxin-mediated cytotoxicity[6].
In vivo, intravenous injection of N-Desethyl amodiaquine (3, 6mg/kg) inhibits PA-LF induced death in the Sprague−Dawley rat model by inhibiting cytosolic entry of LF[6]. Oral administration of N-Desethyl amodiaquine every 12h for 5 days at 5, 10, and 50mg/kg protects mice challenged with B. Anthracis Spores while decreasing survival times at increased N-Desethyl amodiaquine doses[7].
References:
[1] Sasi, P., Abdulrahaman, A., Mwai, L., Muriithi, S., Straimer, J., Schieck, E., Rippert, A., Bashraheil, M., Salim, A., Peshu, J., Awuondo, K., Lowe, B., Pirmohamed, M., Winstanley, P., Ward, S., Nzila, A., & Borrmann, S. (2009). In vivo and in vitro efficacy of amodiaquine against Plasmodium falciparum in an area of continued use of 4-aminoquinolines in East Africa. The Journal of infectious diseases, 199(11), 1575–1582.
[2] Li, X. Q., Björkman, A., Andersson, T. B., Ridderström, M., & Masimirembwa, C. M. (2002). Amodiaquine clearance and its metabolism to N-desethylamodiaquine is mediated by CYP2C8: a new high affinity and turnover enzyme-specific probe substrate. The Journal of pharmacology and experimental therapeutics, 300(2), 399–407.
[3] Mariga, S. T., Gil, J. P., Sisowath, C., Wernsdorfer, W. H., & Björkman, A. (2004). Synergism between amodiaquine and its major metabolite, desethylamodiaquine, against Plasmodium falciparum in vitro. Antimicrobial agents and chemotherapy, 48(11), 4089–4096.
[4] Childs, G. E., Boudreau, E. F., Milhous, W. K., Wimonwattratee, T., Pooyindee, N., Pang, L., & Davidson, D. E., Jr (1989). A comparison of the in vitro activities of amodiaquine and desethylamodiaquine against isolates of Plasmodium falciparum. The American journal of tropical medicine and hygiene, 40(1), 7–11.
[5] DeWald, L. E., Johnson, J. C., Gerhardt, D. M., Torzewski, L. M., Postnikova, E., Honko, A. N., Janosko, K., Huzella, L., Dowling, W. E., Eakin, A. E., Osborn, B. L., Gahagen, J., Tang, L., Green, C. E., Mirsalis, J. C., Holbrook, M. R., Jahrling, P. B., Dyall, J., & Hensley, L. E. (2019). In Vivo Activity of Amodiaquine against Ebola Virus Infection. Scientific reports, 9(1), 20199.
[6] Zilbermintz, L., Leonardi, W., Jeong, S. Y., Sjodt, M., McComb, R., Ho, C. L., Retterer, C., Gharaibeh, D., Zamani, R., Soloveva, V., Bavari, S., Levitin, A., West, J., Bradley, K. A., Clubb, R. T., Cohen, S. N., Gupta, V., & Martchenko, M. (2015). Identification of agents effective against multiple toxins and viruses by host-oriented cell targeting. Scientific reports, 5, 13476.
[7] Martchenko Shilman, M., Bartolo, G., Alameh, S., Peterson, J. W., Lawrence, W. S., Peel, J. E., Sivasubramani, S. K., Beasley, D. W. C., Cote, C. K., Demons, S. T., Halasahoris, S. A., Miller, L. L., Klimko, C. P., Shoe, J. L., Fetterer, D. P., McComb, R., Ho, C. C., Bradley, K. A., Hartmann, S., Cheng, L. W., … West, J. (2021). In Vivo Activity of Repurposed Amodiaquine as a Host-Targeting Therapy for the Treatment of Anthrax. ACS infectious diseases, 7(8), 2176–2191.
N-Desethyl amodiaquine是一种抗寄生虫药物，对疟原虫菌株V1/S和3D7具有抑制作用，其IC50值分别为97nM和25nM[1]。N-Desethyl amodiaquine是抗疟药物阿莫地喹的主要代谢产物，由细胞色素P450 2C8同工酶催化生成[2]。N-Desethyl amodiaquine对恶性疟原虫（Plasmodium falciparum）具有很高的活性，并且可以与阿莫地喹产生协同作用，通常用于疟疾相关研究[3-4]。
在体外实验中，N-Desethyl amodiaquine显著阻断了埃博拉病毒在Huh 7和Vero E6细胞系中的复制，其IC50值分别为2.8μM和11μM[5]。用N-Desethyl amodiaquine（8、16、33或66μM）处理RAW264.7细胞1小时，再用500ng/mL保护性抗原（PA)+ 500ng/mL致死因子( LF)处理6h，以剂量依赖的方式抑制了蛋白酶B的活性，并减少了毒素介导的细胞毒性[6]。
在体内实验中，在Sprague-Dawley大鼠模型中，静脉注射N-Desethyl amodiaquine（3、6mg/kg）可通过抑制致死因子（LF）进入细胞质而抑制LF-PA诱导的死亡[6]。此外，口服给予N-Desethyl amodiaquine（每12小时一次，连续5天，剂量为5、10和50mg/kg）可保护感染炭疽芽孢杆菌孢子的小鼠，但随着N-Desethyl amodiaquine剂量的增加，生存时间会缩短[7]。
| Cell experiment [1]: | |
Cell lines | RAW264.7 cells |
Preparation Method | RAW264.7 cells untreated with drugs were lysed, and equal amount of cathepsin B containing protein lysate was added to the substrate solution with and without AQ, CQ, N-Desethyl amodiaquine, or DECQ at concentrations of 4, 8, 16, 33, or 66μM. Cellular cathepsin B activity with and without drugs was tested by pre-treating cells with drugs for 1 hour, followed by lysing cells and testing cathepsin B activity with a fluorescently labeled substrate. The activity of 0.5ng/μl of purified human cathepsin B was mixed with and without drugs without pre-incubation and detected with a fluorescently labeled substrate. Fluorescence intensity indicating cathepsin B activity was measured at an excitation wavelength of 370nm and emission wave length of 450nm. |
Reaction Conditions | 8, 16, 33, or 66μM; 1h |
Applications | N-Desethyl amodiaquine inhibited proteinase B activity in a dose-dependent manner. |
| Animal experiment [1]: | |
Animal models | Sprague-Dawley rats |
Preparation Method | Five Male Sprague-Dawley rats (226 to 250g; Charles River) per group were used. Animals were injected intravenously with a lethal dose of anthrax toxin (LD100) and were intravenously co-injected with N-Desethyl amodiaquine at 1.5, 3.0, or 6.0mg/kg. Rats were monitored for signs of clinical illness or death for 14 days after the challenge. |
Dosage form | 1.5, 3.0, or 6.0mg/kg ; i.v. |
Applications | N-Desethyl amodiaquine(3,6mg/kg) inhibits LF-PA-induced death by Inhibiting cytosolic entry of LF. |
References: | |
| Cas No. | 79352-78-6 | SDF | |
| 别名 | 去乙基阿莫地喹 | ||
| Canonical SMILES | OC1=CC=C(NC2=CC=NC3=CC(Cl)=CC=C23)C=C1CNCC | ||
| 分子式 | C18H18ClN3O | 分子量 | 327.81 |
| 溶解度 | DMSO: 125 mg/mL (381.32 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.0505 mL | 15.2527 mL | 30.5055 mL |
| 5 mM | 0.6101 mL | 3.0505 mL | 6.1011 mL |
| 10 mM | 0.3051 mL | 1.5253 mL | 3.0505 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >98.00%
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