丙脒腙

制备生物活性体外研究体内研究

丙脒腙

CAS号:459-86-9
英文名:Mitoguazone
中文名:丙脒腙
CBNumber:CB01179220
分子式:C5H12N8
分子量:184.2
MOL File:459-86-9.mol

丙脒腙化学性质

熔点 :225 °C (decomp)
沸点 :323.8±25.0 °C(Predicted)
密度 :1.55±0.1 g/cm3(Predicted)
储存条件 :Store at -20°C
酸度系数(pKa) :7.63, 9.05(at 25℃)
水溶解性 :Water: 50 mg/mL (271.44 mM; ultrasonic and adjust pH to 9 with HCl)
CAS 数据库 :459-86-9

丙脒腙性质、用途与生产工艺

制备米托胍腙的合成方法：在配有回流冷凝器、温度计、滴液漏斗、磁力搅拌器的500ml四口烧瓶中加入氨基胍碳酸盐、甲醇（可或回收），开机搅拌，在22~28℃用2小时滴加浓盐酸使PH=1，盐酸滴加完毕在22~30℃继续搅拌30分钟，缓慢升温到60±2℃并维持30分钟后，降温到22~28℃，用3小时滴加丙酮醛缩二甲醇，滴加丙酮醛缩二甲醇的过程中保持温度在22~28℃，丙酮醛缩二甲醇滴加完毕继续搅拌过夜，次日反应液冷至5~10℃，过滤，用甲醇洗涤3次，每次10ml。滤液经常压回收重复使用；滤饼浸泡于100ml甲醇中，经洗涤过滤、真空干燥，得米托胍腙，纯度高达（HPLC）99.5%以上。
生物活性 Mitoguazone (Methylglyoxal-bis(guanylhydrazone)) 是一种具有有效抗肿瘤活性的合成多羰基衍生物。Mitoguazone 是一种可透过血脑屏障的竞争性的 S-腺苷-蛋氨酸脱羧酶 (S-adenosyl-methionine decarboxylase) 抑制剂，可破坏多胺的生物合成。Mitoguazone 诱导细胞凋亡 (apoptosis)，可抑制 HIV DNA 整合到单核细胞和巨噬细胞中的细胞 DNA 中。Mitoguazone 具可用于急性白血病，霍奇金淋巴瘤和非霍奇金淋巴瘤的研究。
体外研究

Mitoguazone competitively inhibits spermidine synthesis in lymphocytes at concentrations as low as 0.5 μg/mL. Levels of 30 μg/mL or more inhibit protein synthesis and mitochondrial respiration.
The ability of Mitoguazone to induce apoptosis by inhibiting the polyamine pathway is assessed in three Burkitt's lymphoma cell lines (Raji, Ramos and Daudi) and one prostate carcinoma cell line (MPC 3). Mitoguazone induces apoptosis in all the different human cancer cell lines tested in a concentration- and time-dependent way, and triggers a p53-independent programmed cell death in the human breast cancer MCF7 cell line.
体内研究

The influence of different stages of leukemia P388 on the pharmacokinetics of the antineoplastic agent Mitoguazone in mice is investigated. Independent of the tumor stage investigated, the total clearance of mitoguazone is slightly reduced reflecting a moderate increase of AUC in the serum of leukemia-bearing animals. Furthermore, in an advanced tumor stage the drug levels in kidneys, liver, spleen and serum are found to be elevated to some extent in comparison to tumor-free controls in contrast to an earlier stage of leukemia.
化学性质白色结晶，熔点256-257℃（分解）。极易溶于水，在酸性水中较稳定，在碱性介质中不稳定。
用途该品为治疗成人急性粒细胞白血病和恶性淋巴瘤的药物。
生产方法由氨基胍碳酸盐（见02050）缩合而得。将氨基脲碳酸盐溶于无水乙醇，在室温下滴加盐酸，回流反应1h后冷却至30℃，继续滴加盐酸。冷却至0℃，滴加丙酮醛。加毕，反应6h。放置冷却，过滤，滤饼经洗涤、干燥、精制而得丙脒腙。收率约65%。