Diaveridine (EGIS-5645)
(Synonyms: 二氨藜芦啶; EGIS-5645) 目录号 : GC32343
A DHFR inhibitor with antimicrobial activity
Cas No.:5355-16-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | Cells are cultured at 37°C in a humidified atmosphere of 5% CO2 in air. The growth medium is Eagle’s MEM supplemented with 10% fetal bovine serum. In the experiment without metabolic activation, the cells are treated for 24 or 48 h continuously without a medium change. In the experiment with metabolic activation, the cells are pulse treated with test compounds (including Diaveridine) at varying doses for 6 h and incubated for 18 h in fresh culture medium. Breakage type chromatid aberrations, exchange type chromatid aberrations, breakage type chromosome aberrations, and exchange type chromosome aberrations are scored. Gaps are also counted. Mitotic index is determined from scoring 2000 cells[2]. |
Animal experiment: | 3]Fifty male ICR mice, weighing 25 to 35 g, are assigned to five groups randomly with 10 mice in each group. Mice in the experiment groups receive Diaveridine (DVD) via IG at ed 128 mg/kg (low doses), 256 mg/kg (medium doses), and 512 mg/kg (high doses) body weight for 5 consecutive days, respectively. Mice in negative and positive control groups receive IG 1% CMC-Na solvent and 40 mg/kg body weight of cyclophosphamide, respectively. The testing groups are administered 0.2 mL/10 g Diaveridine (mixed with 1% of CMC-Na, to obtain the concentration of 2 mg/mL.) body weight, once a day, for 5 days. The behavioral changes are recorded on the daily basis[3]. |
References: [1]. Sirichaiwat C et al. Target guided synthesis of 5-benzyl-2,4-diamonopyrimidines: their antimalarial activities and binding affinities to wild type and mutant dihydrofolate reductases from Plasmodium falciparum. J Med Chem 47:345-54 (2004). | |
Diaveridine is a dihydrofolate reductase (DHFR) inhibitor (Ki = 11.5 nM for the P. falciparum enzyme) with antimicrobial activity.1,2,3,4 It is active against P. vulgaris, S. aureus, and S. pyogenes in vitro (MICs = 4, 1, and 2 μg/ml, respectively).2 Diaveridine has anticoccidial activity when administered alone or in combination with sulfaquinoxaline.3,4
1.Sirichaiwat, C., Intraraudom, C., Kamchonwongpaisan, S., et al.Target guided synthesis of 5-benzyl-2,4-diamonopyrimidines: Their antimalarial activities and binding affinities to wild type and mutant dihydrofolate reductases from Plasmodium falciparumJ. Med. Chem.47(2)345-354(2004) 2.Roth, B., Falco, E.A., Hitchings, G.H., et al.5-Benzyl-2,4-diaminopyrimidines as antibacterial agents. I. Synthesis and antibacterial activity in vitroJ. Med. Chem.5(6)1103-1123(1962) 3.Ryley, J.F., and Betts, M.J.Chemotherapy of chicken coccidiosisAdvances in Pharmacology11221-293(1973) 4.Wang, J., Sun, F., Tang, S., et al.Acute, mutagenicity, teratogenicity and subchronic oral toxicity studies of diaveridine in rodentsEnviron. Toxicol. Pharmacol.40(2)660-670(2015)
| Cas No. | 5355-16-8 | SDF | |
| 别名 | 二氨藜芦啶; EGIS-5645 | ||
| Canonical SMILES | NC1=NC=C(CC2=CC=C(OC)C(OC)=C2)C(N)=N1 | ||
| 分子式 | C13H16N4O2 | 分子量 | 260.29 |
| 溶解度 | DMSO : 32 mg/mL (122.94 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 | 3.8419 mL | 19.2093 mL | 38.4187 mL |
| 5 mM | 0.7684 mL | 3.8419 mL | 7.6837 mL |
| 10 mM | 0.3842 mL | 1.9209 mL | 3.8419 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。
The genotoxicity of Diaveridine and trimethoprim
Environ Toxicol Pharmacol 1997 Sep;3(4):297-306.PMID:21781790DOI:10.1016/s1382-6689(97)00026-4.
We examined the genotoxicity of Diaveridine and trimethoprim in the bacterial umu test, the bacterial reverse mutation test, the in vitro chromosome aberration test, the in vivo rodent bone marrow micronucleus test in two species, and the in vivo comet assay in five mouse organs. Both compounds were negative in the umu test (Salmonella typhimurium TA1535/pSK1002) and in the reverse mutation tests (S. typhimurium TA100, TA98, TA97, TA102, and Escherichia coli WP2 uvrA/pKM101) in the presence and absence of S9 mix. Diaveridine induced structural chromosome aberrations in cultured Chinese hamster CHL cells in the absence of a metabolic activation system, but not in the presence of a liver S9 fraction. No clastogenic activity in CHL cells was detected for trimethoprim. Bone marrow micronucleus tests in mice and rats conducted on Diaveridine by single- and triple-oral dosing protocols were negative. The comet assay revealed that a single oral administration of Diaveridine significantly induced DNA damage in liver, kidney, lung, and spleen cells, but not in bone marrow cells. The significant increase in migration values of DNA was reproducible with dose-response relationship. We suggest that the liver detoxifies the compound before it reaches the bone marrow, and that is why it is negative in the in vivo bone marrow micronucleus test. We concluded that Diaveridine is genotoxic to mammalian cells in vitro and in vivo.
Acute and sub-chronic toxicity study of Diaveridine in Wistar rats
Regul Toxicol Pharmacol 2015 Oct;73(1):232-40.PMID:26209270DOI:10.1016/j.yrtph.2015.07.010.
Diaveridine, a developed dihydrofolate reductase inhibitor, has been widely used as anticoccidial drug and antibacterial synergist. However, few studies have been performed to investigate its toxicity. To provide detailed toxicity with a wide spectrum of doses for Diaveridine, acute and sub-chronic toxicity studies were conducted. Calculated LD50 was 2330 mg/kg b.w. in females and 3100 mg/kg b.w. in males, and chromodacryorrhea was noted in some females before their death. In the sub-chronic study, Diaveridine was fed to Wistar rats during 90 days at dietary levels of 0, 23, 230, 1150 and 2000 mg/kg, which were about 0, 2.0-2.3, 21.0-23.5, 115.2-126.9 and 212.4-217.9 mg/kg b.w., respectively. Significant decrease in body weights in both genders at 1150 and 2000 mg/kg groups and significant increases in relative weights of brain in both genders, liver in females, kidneys and testis in males, alkaline phosphatase and potassium in both genders at 2000 mg/kg diet were noted. Significant decrease in absolute weights of several organs, hemoglobin and red blood cell count in both genders, albumin and total protein in females were observed at 2000 mg/kg diet. Fibroblasts in the kidneys, cell swelling of the glomerular zone in the adrenals and inflammation in the liver were found at 2000 mg/kg group. The no-observed-adverse-effect level of Diaveridine was 230 mg/kg diet (21.0-23.5 mg/kg b.w./day).
A new antiinflammatory agent (EGIS-5645) without gastrointestinal side-effect
Agents Actions Suppl 1991;32:39-43.PMID:1906236DOI:10.1007/978-3-0348-7405-2_4.
The compound EGIS-5645 is a potent antipyretic agent possessing analgesic and antiinflammatory properties. The drug is active in antiinflammatory models such as carrageenin oedema and adjuvant arthritis. EGIS-5645 shows practically no gastro-ulcerogenic effect. The molecule does not inhibit either prostaglandin biosynthesis or soybean lipoxygenase enzyme activity.
Development of radioactive tracing coupled with LC/MS-IT-TOF methodology for the discovery and identification of Diaveridine metabolites in pigs
Food Chem 2021 Nov 30;363:130200.PMID:34120054DOI:10.1016/j.foodchem.2021.130200.
We developed a sensitive and reliable method by coupling radiotracing with LC/MS-IT-TOF to identify Diaveridine metabolites. Tritium-labeled Diaveridine was orally administered to pigs and their organs, blood, bile, and excreta were collected. Under optimized conditions, radioactive recovery was >90% and the highest numbers of metabolites were detected. MCX-based solid-phase extraction was conducted for urine, plasma, and bile purification. Methanol-chloroform 1:1 (v/v), methanol-chloroform 6:1 (v/v), methanol, methanol-chloroform 1:1 (v/v), and methanol were used as solvents to extract feces, liver, kidney, fat and muscle, respectively. The method validation confirmed satisfactory 3H-H exchange efficiency (<5%), chromatographic column efficiency (鈮?7.5%), LOQ (10.73 渭g/kg), and analytical accuracy (97.6-107.8%) and precision (RSD < 5%). Moreover, novel in vivo metabolites were detected in the pigs, including D2 (3'-desmethyl-diaveridine monoglucuronide), D3 (Diaveridine monoglucuronide). Hence, the analytical method developed herein lays an empirical foundation for further systematic studies of the Diaveridine metabolism.
Determination of sulphachloropyrazine-diaveridine residues by high performance liquid chromatography in broiler edible tissues
J Vet Med Sci 2016 Jan;77(12):1555-63.PMID:26212255DOI:10.1292/jvms.14-0605.
Diaveridine (DVD) is used in combination with sulphachloropyrazine (SPZ) as an effective antibacterial agent and antiprotozoal agent, respectively, in humans and animals. To gain a better understanding of the metabolism of SPZ and DVD in the food-producing animals, a high performance liquid chromatography (HPLC) method to determine and quantify sulphachloropyrazine (SPZ) and Diaveridine (DVD) suspension residues from broilers is reported. Thirty healthy chickens were orally administered with sulphachloropyrazine-diaveridine (SPZ-DVD) suspension in water of 300 mg/l (SPZ) per day for seven successive days. Six chickens per day were slaughtered at 0, 1, 3, 5 and 7 days after the last administration. This procedure permitted SPZ and DVD to be separated from muscle tissue, liver, kidneys and skin with fat after extraction with acetonitrile and acetone under slightly acidic conditions. From the detected residuals in different tissues, we found that SPZ was quickly eliminated in liver and muscle, and slowly eliminated in kidney and skin with fat. DVD was quickly eliminated in liver and slowly eliminated in kidney. The withdrawal period of SPZ was 3.26, 3.72, 4.39 and 5.43 days in muscle, liver, kidney and skin with fat, respectively. The withdrawal period of DVD was 4.77, 4.94, 6.74 and 4.58 days in muscle, liver, kidney and skin with fat, respectively. Therefore, the suggested withdrawal period for SPZ-DVD suspension should be 7 days after dosing for seven successive days.