Thiocarlide
(Synonyms: 戊氧苯硫脲,Isoxyl) 目录号 : GC45037An antimycobacterial tuberculosis drug
Cas No.:910-86-1
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
Thiocarlide (isoxyl) is a thiourea derivative that was used in the 1960s to successfully treat tuberculosis (TB). It has considerable antimycobacterial activity in vitro and is effective against multi-drug resistant strains of Mycobacterium tuberculosis in the range of 1-10 µg/ml. [1] [2] At concentrations of 10 µM, isoxyl inhibits the synthesis of M. bovis during six hours of exposure which is similar to isoniazid (INH) and ethionamide (ETH), two other predominant anti-tuberculosis drugs. Unlike INH and ETH, isoxyl also partially inhibits the synthesis of fatty acids. Isoxyl shows no acute toxicity against primary macrophage cell cultures as demonstrated by diminution of redox activity.[2]
Reference:
[1]. Phetsuksiri, B., Jackson, M., Scherman, H., et al. Unique mechanism of action of the thiourea drug isoxyl on mycobacterium tuberculosis. The Journal of Biological Chemisty 278(52), 53123-53130 (2003).
[2]. Phetsuksiri, B., Baulard, A.R., Cooper, A.M., et al. Antimycobacterial activities of isoxyl and new derivatives through the inhibition of mycolic acid synthesis. Antimicrobial Agents and Chemotherapy 43(5), 1042-1051 (1999).
| Cas No. | 910-86-1 | SDF | |
| 别名 | 戊氧苯硫脲,Isoxyl | ||
| 化学名 | N,N'-bis[4-(3-methylbutoxy)phenyl]-thiourea | ||
| Canonical SMILES | CC(C)CCOc1ccc(cc1)NC(=S)Nc1ccc(OCCC(C)C)cc1 | ||
| 分子式 | C23H32N2O2S | 分子量 | 400.6 |
| 溶解度 | DMF: 30 mg/ml, DMSO: 30 mg/ml, Ethanol: 1 mg/ml | 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 | 2.4963 mL | 12.4813 mL | 24.9626 mL |
| 5 mM | 0.4993 mL | 2.4963 mL | 4.9925 mL |
| 10 mM | 0.2496 mL | 1.2481 mL | 2.4963 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。
N-D-aldopentofuranosyl-N'-[p-(isoamyloxy)phenyl]-thiourea derivatives: potential anti-TB therapeutic agents
Bioorg Med Chem Lett 2008 Apr 15;18(8):2649-51.PMID:18362068DOI:10.1016/j.bmcl.2008.03.033.
Thiocarlide (THC; N,N'-bis[p-(isoamyloxy)phenyl]-thiourea; also known as isoxyl) has been used in the past as anti-tuberculosis agent. In an effort to improve the therapeutic value of THC several N-pentofuranosyl-N'-[p-(isoamyloxy)phenyl]-thiourea derivatives were synthesized by coupling of an aniline derivative and pentofuranosyl isothiocyanates. The MIC values of the new products against M.tb indicate that this new approach to the synthesis of potential anti-TB therapeutic agents was successful.
A Histoplasma capsulatum Lipid Metabolic Map Identifies Antifungal Targets
mBio 2021 Dec 21;12(6):e0297221.PMID:34809453DOI:10.1128/mBio.02972-21.
Lipids play a fundamental role in fungal cell biology, being essential cell membrane components and major targets of antifungal drugs. A deeper knowledge of lipid metabolism is key for developing new drugs and a better understanding of fungal pathogenesis. Here, we built a comprehensive map of the Histoplasma capsulatum lipid metabolic pathway by incorporating proteomic and lipidomic analyses. We performed genetic complementation and overexpression of H. capsulatum genes in Saccharomyces cerevisiae to validate reactions identified in the map and to determine enzymes responsible for catalyzing orphan reactions. The map led to the identification of both the fatty acid desaturation and the sphingolipid biosynthesis pathways as targets for drug development. We found that the sphingolipid biosynthesis inhibitor myriocin, the fatty acid desaturase inhibitor Thiocarlide, and the fatty acid analog 10-thiastearic acid inhibit H. capsulatum growth in nanomolar to low-micromolar concentrations. These compounds also reduced the intracellular infection in an alveolar macrophage cell line. Overall, this lipid metabolic map revealed pathways that can be targeted for drug development. IMPORTANCE It is estimated that 150 people die per hour due to the insufficient therapeutic treatments to combat fungal infections. A major hurdle to developing antifungal therapies is the scarce knowledge on the fungal metabolic pathways and mechanisms of virulence. In this context, fungal lipid metabolism is an excellent candidate for developing drugs due to its essential roles in cellular scaffolds, energy storage, and signaling transductors. Here, we provide a detailed map of Histoplasma capsulatum lipid metabolism. The map revealed points of this fungus lipid metabolism that can be targeted for developing antifungal drugs.
Ethionamide activation and sensitivity in multidrug-resistant Mycobacterium tuberculosis
Proc Natl Acad Sci U S A 2000 Aug 15;97(17):9677-82.PMID:10944230DOI:10.1073/pnas.97.17.9677.
Ethionamide (ETA) is an important component of second-line therapy for the treatment of multidrug-resistant tuberculosis. Synthesis of radiolabeled ETA and an examination of drug metabolites formed by whole cells of Mycobacterium tuberculosis (MTb) have allowed us to demonstrate that ETA is activated by S-oxidation before interacting with its cellular target. ETA is metabolized by MTb to a 4-pyridylmethanol product remarkably similar in structure to that formed by the activation of isoniazid by the catalase-peroxidase KatG. We have demonstrated that overproduction of Rv3855 (EtaR), a putative regulatory protein from MTb, confers ETA resistance whereas overproduction of an adjacent, clustered monooxygenase (Rv3854c, EtaA) confers ETA hypersensitivity. Production of EtaA appears to be negatively regulated by EtaR and correlates directly with [(14)C]ETA metabolism, suggesting that EtaA is the activating enzyme responsible for thioamide oxidation and subsequent toxicity. Coding sequence mutations in EtaA were found in 11 of 11 multidrug-resistant MTb patient isolates from Cape Town, South Africa. These isolates showed broad cross-resistance to thiocarbonyl containing drugs including ETA, thiacetazone, and Thiocarlide.
Scalable and Phosphine-Free Conversion of Alcohols to Carbon-Heteroatom Bonds through the Blue Light-Promoted Iodination Reaction
J Org Chem 2020 Mar 6;85(5):3717-3727.PMID:32019308DOI:10.1021/acs.joc.9b03373.
One of the fundamental and highly valuable transformations in organic chemistry is the nucleophilic substitution of alcohols. Traditionally, these reactions require strategies that employ stoichiometric hazardous reagents and are associated with difficulty in purification of the by-products. To overcome these challenges, here, we report a simple route toward the diverse conversion of alcohols via an SN2 pathway, in which blue light-promoted iodination is used to form alkyl iodide intermediates from simple unreactive alcohols. The scope of the process tolerates a range of nucleophiles to construct C-N, C-O, C-S, and C-C bonds. Furthermore, we also demonstrate that this method can be used for the preparation and late-stage functionalization of pharmaceuticals, as highlighted by the syntheses of Thiocarlide, butoxycaine, and pramoxine.
Antimycobacterial activities of isoxyl and new derivatives through the inhibition of mycolic acid synthesis
Antimicrob Agents Chemother 1999 May;43(5):1042-51.PMID:10223912DOI:10.1128/AAC.43.5.1042.
Isoxyl (ISO), a thiourea (Thiocarlide; 4, 4'-diisoamyloxythiocarbanilide), demonstrated potent activity against Mycobacterium tuberculosis H37Rv (MIC, 2.5 micrograms/ml), Mycobacterium bovis BCG (MIC, 0.5 microgram/ml), Mycobacterium avium (MIC, 2.0 microgram/ml), and Mycobacterium aurum A+ (MIC, 2.0 microgram/ml), resulting in complete inhibition of mycobacteria grown on solid media. Importantly, a panel of clinical isolates of M. tuberculosis from different geographical areas with various drug resistance patterns were all sensitive to ISO in the range of 1 to 10 microgram/ml. In a murine macrophage model, ISO exhibited bactericidal killing of viable intracellular M. tuberculosis in a dose-dependent manner (0.05 to 2.50 microgram/ml). The selective action of ISO on mycolic acid synthesis was studied through the use of [1, 2-14C]acetate labeling of M. tuberculosis H37Rv, M. bovis BCG, and M. aurum A+. At its MIC for M. tuberculosis, ISO inhibited the synthesis of both fatty acids and mycolic acids (alpha-mycolates by 91.6%, methoxymycolates by 94.3%, and ketomycolates by 91.1%); at its MIC in M. bovis BCG, ISO inhibited the synthesis of alpha-mycolates by 87.2% and that of ketomycolates by 88.5%; and the corresponding inhibitions for M. aurum A+ were 87.1% for alpha-mycolates, 87.2% for ketomycolates, and 86.5% for the wax-ester mycolates. A comparison with isoniazid (INH) and ethionamide (ETH) demonstrated marked similarity in action, i.e., inhibition of the synthesis of all kinds of mycolic acids. However, unlike INH and ETH, ISO also inhibited the synthesis of shorter-chain fatty acids. ISO showed no acute toxicity against primary macrophage cell cultures as demonstrated by diminution of redox activity. A homologous series of ISO derivatives were synthesized. Most derivatives were as effective or more effective than the parent compound in the agar proportion assay. Thus, these thioureas, like INH and ETH, specifically inhibit mycolic acid synthesis and show promise in counteracting a wide variety of drug-sensitive and -resistant strains of M. tuberculosis.