Hycanthone
(Synonyms: 海恩酮) 目录号 : GC32096
Hycanthone是一种有效的抗血吸虫药物。
Cas No.:3105-97-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | Appropriate quantities of Hycanthone (1 to 100 μg) in 10 mL maintenance medium are added to plastic flasks (75 cm2) containing approximately 3×107 LLC-MK2 cells in monolayer, which are then incubated at 35°C for 24 h. Maintenance medium is decanted, and 2 mL influenza virus is added onto cell monolayers and incubated at 35°C for 2 h. The multiplicity of infection is approximately 1.0. Inoculum is removed and 10 mL maintenance medium is added to each flask, which is then incubated at 35°C for 24 h. Supernatant fluid is decanted, centrifuged at 100,000 g for 1 h, dialyzed against HCI-KCI buffer (pH 2.0) at 4°C for 24 h, and then dialyzed against two changes of phosphate-buffered saline (pH 7.1) at 4°C for 24 h. Fluids are passed through filters to obtain sterile preparations. Samples are stored at -80°C until assayed for interferon activity[2]. |
Animal experiment: | Female outbred Swiss albino mice used as definitive hosts weigh 18 to 20 g at the time of infection. Hycanthone is administered at 0.01 mL/g body weight intramuscularly by splitting the dose into the two hind legs, so that each mouse receives 80 mg/kg body weight of the free base. Treatments are usually performed during the 8th week after infection[1]. |
References: [1]. Pica Mattoccia L, et al. Effect of hycanthone administered in vivo upon the incorporation of radioactive precursors into macromolecules of Schistosoma mansoni. Mol Biochem Parasitol. 1983 Jun;8(2):99-107. | |
Hycanthone is an effective antischistosomai drug.
Hycanthone at 20 mg/mL or more is progressively more detrimental to cell viability. Results reveal that increased concentrations of Hycanthone, ranging from 0.1 to 10 μg/mL, progressively reduces viral interferon yields as much as 73% compare to that of controls[2].
Results show that the incorporation of tritiated thymidine into TCA-precipitable material of adult sensitive worms undergo a progressive decrease after treatment with Hycanthone. Immature worms are totally unaffected by Hycanthone at all times tested. Male worms treated with Hycanthone show signs of a possible partial recovery from the initial low levels of incorporation. The incorporation of tritiated leucine by drug-sensitive worms treated with Hycanthone is inhibited by 40 to 50% in the first four days after treatment. Results show that, 7 days after Hycanthone treatment, both ribosomal RNA species are reduced by at least 80% with respect to untreated worms, with some indication of a possible accumulation of heavier precursor molecules[1].
[1]. Pica Mattoccia L, et al. Effect of hycanthone administered in vivo upon the incorporation of radioactive precursors into macromolecules of Schistosoma mansoni. Mol Biochem Parasitol. 1983 Jun;8(2):99-107. [2]. Hahon N, et al. Action of antischistosomal drugs, hycanthone and its analog 1A-4 N-oxide, on viral interferon induction. J Toxicol Environ Health. 1980 Jul;6(4):705-12.
| Cas No. | 3105-97-3 | SDF | |
| 别名 | 海恩酮 | ||
| Canonical SMILES | O=C1C2=C(SC3=C1C=CC=C3)C(CO)=CC=C2NCCN(CC)CC | ||
| 分子式 | C20H24N2O2S | 分子量 | 356.48 |
| 溶解度 | DMSO : 30 mg/mL (84.16 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 | 2.8052 mL | 14.026 mL | 28.0521 mL |
| 5 mM | 0.561 mL | 2.8052 mL | 5.6104 mL |
| 10 mM | 0.2805 mL | 1.4026 mL | 2.8052 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。
Hycanthone Inhibits Inflammasome Activation and Neuroinflammation-Induced Depression-Like Behaviors in Mice
Biomol Ther (Seoul) 2023 Mar 1;31(2):161-167.PMID:36203404DOI:10.4062/biomolther.2022.073.
Despite the various medications used in clinics, the efforts to develop more effective treatments for depression continue to increase in the past decades mainly because of the treatment-resistant population, and the testing of several hypotheses- and target-based treatments. Undesirable side effects and unresponsiveness to current medications fuel the drive to solve this top global health problem. In this study, we focused on neuroinflammatory response-mediated depression which represents a cluster of depression etiology both in animal models and humans. Several meta-analyses reported that proinflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were increased in major depressive disorder patients. Inflammatory mediators implicated in depression include type-I interferon and inflammasome pathways. To elucidate the molecular mechanisms of neuroinflammatory cascades underlying the pathophysiology of depression, we introduced Hycanthone, an antischistosomal drug, to check whether it can counteract depressive-like behaviors in vivo and normalize the inflammation-induced changes in vitro. Lipopolysaccharide (LPS) treatment increased proinflammatory cytokine expression in the murine microglial cells as well as the stimulation of type I interferon-related pathways that are directly or indirectly regulated by Janus kinase-signal transducer and activator of transcription (JAK-STAT) activation. Hycanthone treatment attenuated those changes possibly by inhibiting the JAK-STAT pathway and inflammasome activation. Hycanthone also ameliorated depressive-like behaviors by LPS. Taken together, we suggest that the inhibitory action of Hycanthone against the interferon pathway leading to attenuation of depressive-like behaviors can be a novel therapeutic mechanism for treating depression.
Molecular basis for Hycanthone drug action in schistosome parasites
Mol Biochem Parasitol 2020 Mar;236:111257.PMID:32027942DOI:10.1016/j.molbiopara.2020.111257.
Hycanthone (HYC) is a retired drug formerly used to treat schistosomiasis caused by infection from Schistosoma mansoni and S. haematobium. Resistance to HYC was first observed in S. mansoni laboratory strains and in patients in the 1970s and the use of this drug was subsequently discontinued with the substitution of praziquantel (PZQ) as the single antischistosomal drug in the worldwide formulary. In endemic regions, multiple organizations have partnered with the World Health Organization to deliver PZQ for morbidity control and prevention. While the monotherapy reduces the disease burden, additional drugs are needed to use in combination with PZQ to stay ahead of potential drug resistance. HYC will not be reintroduced into the schistosomiasis drug formulary as a combination drug because it was shown to have adverse properties including mutagenic, teratogenic and carcinogenic activities. Oxamniquine (OXA) was used to treat S. mansoni infection in Brazil during the brief period of HYC use, until the 1990s. Its antischistosomal efficacy has been shown to work through the same mechanism as HYC and it does not possess the undesirable properties linked to HYC. OXA demonstrates cross-resistance in Schistosoma strains with HYC resistance and both are prodrugs requiring metabolic activation in the worm to toxic sulfated forms. The target activating enzyme has been identified as a sulfotransferase enzyme and is currently used as the basis for a structure-guided drug design program. Here, we characterize the sulfotransferases from S. mansoni and S. haematobium in complexes with HYC to compare and contrast with OXA-bound sulfotransferase crystal structures. Although HYC is discontinued for antischistosomal treatment, it can serve as a resource for design of derivative compounds without contraindication.
Hycanthone: a frameshift mutagen
Science 1971 Jun 4;172(3987):1058-60.PMID:5573958DOI:10.1126/science.172.3987.1058.
Rapid spot-test screening of antischistosomal agents reveals that Hycanthone is a potent frameshift mutagen while the closely related compound, miracil D, is nonmutagenic in Salmonella. Both Hycanthone and miracil D are frameshift mutagens for T4 bacteriophage during growth in Escherichia coli.
Resistance of schistosomes to Hycanthone and oxamniquine
Mem Inst Oswaldo Cruz 1989 Oct;84 Suppl 1:38-45.PMID:2638729DOI:10.1590/s0074-02761989000500005.
Genetic crosses between phenotypically resistant and sensitive schistosomes demonstrated that resistance to Hycanthone and oxamniquine behaves like a recessive trait, thus suggesting that resistance is due to the lack of some factor. We hypothesized that, in order to kill schistosomes, Hycanthone and oxamniquine need to be converted into an active metabolite by some parasite enzyme which, if inactive, results in drug resistance. Esterification of the drugs seemed to be the most likely event as it would lead to the production of an alkylating agent upon dissociation of the ester. An artificial ester of Hycanthone was indeed active even in resistant worms, thus indirectly supporting our hypothesis. In addition, several lines of evidence demonstrated that exposure to Hycanthone and oxamniquine results in alkylation of worm macromolecules. Thus, radioactive drugs formed covalent bonds with the DNA of sensitive (but not of resistant) schistosomes; an antiserum raised against Hycanthone detected the presence of the drug in the purified DNA fraction of sensitive (but not of resistant) schistosomes; a drug-DNA adduct was isolated from hycanthone-treated worms and fully characterized as hycanthone-deoxyguanosine.
Lucanthone and its derivative Hycanthone inhibit apurinic endonuclease-1 (APE1) by direct protein binding
PLoS One 2011;6(9):e23679.PMID:21935361DOI:10.1371/journal.pone.0023679.
Lucanthone and Hycanthone are thioxanthenone DNA intercalators used in the 1980s as antitumor agents. Lucanthone is in Phase I clinical trial, whereas Hycanthone was pulled out of Phase II trials. Their potential mechanism of action includes DNA intercalation, inhibition of nucleic acid biosyntheses, and inhibition of enzymes like topoisomerases and the dual function base excision repair enzyme apurinic endonuclease 1 (APE1). Lucanthone inhibits the endonuclease activity of APE1, without affecting its redox activity. Our goal was to decipher the precise mechanism of APE1 inhibition as a prerequisite towards development of improved therapeutics that can counteract higher APE1 activity often seen in tumors. The IC(50) values for inhibition of APE1 incision of depurinated plasmid DNA by lucanthone and Hycanthone were 5 µM and 80 nM, respectively. The K(D) values (affinity constants) for APE1, as determined by BIACORE binding studies, were 89 nM for lucanthone/10 nM for Hycanthone. APE1 structures reveal a hydrophobic pocket where hydrophobic small molecules like thioxanthenones can bind, and our modeling studies confirmed such docking. Circular dichroism spectra uncovered change in the helical structure of APE1 in the presence of lucanthone/Hycanthone, and notably, this effect was decreased (Phe266Ala or Phe266Cys or Trp280Leu) or abolished (Phe266Ala/Trp280Ala) when hydrophobic site mutants were employed. Reduced inhibition by lucanthone of the diminished endonuclease activity of hydrophobic mutant proteins (as compared to wild type APE1) supports that binding of lucanthone to the hydrophobic pocket dictates APE1 inhibition. The DNA binding capacity of APE1 was marginally inhibited by lucanthone, and not at all by Hycanthone, supporting our hypothesis that thioxanthenones inhibit APE1, predominantly, by direct interaction. Finally, lucanthone-induced degradation was drastically reduced in the presence of short and long lived free radical scavengers, e.g., TRIS and DMSO, suggesting that the mechanism of APE1 breakdown may involve free radical-induced peptide bond cleavage.