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| Targets |
leishmaniasis; parasites
The primary target of dehydroemetine is the protein synthesis machinery of Entamoeba histolytica, the protozoan parasite responsible for amoebiasis. The compound inhibits protein synthesis by binding to the ribosome and interfering with the translation process, thereby disrupting parasite growth and replication. Unlike emetine, dehydroemetine has been shown to lack significant inhibition of the hERG potassium channel, which may explain its reduced cardiovascular toxicity. The compound also displays activity affecting the mitochondrial membrane potential, suggesting it may have additional targets or mechanisms of action beyond protein synthesis inhibition. This multimodal mechanism could contribute to its antiprotozoal activity and may be relevant for its potential repositioning in malaria treatment. The compound's selectivity for parasitic versus host protein synthesis is a key feature of its antiprotozoal activity. |
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| ln Vitro |
Dehydroemetine is a pyridoisoquinoline which was developed in response to the cardiovascular toxicity associated with emetine and results from the dehydrogenation of the heterotricylic ring of emetine. It is an antiprotozoal agent and displays antimalarial, antiamoebic, and antileishmanial properties. It has a role as an antiprotozoal drug, an antimalarial and an antileishmanial agent.
In vitro, dehydroemetine demonstrates antiprotozoal activity against Entamoeba histolytica by inhibiting protein synthesis and disrupting parasite growth. The compound has also been evaluated for its activity against malaria parasites, suggesting potential for repositioned use. Dehydroemetine shows activity affecting the mitochondrial membrane potential, indicating a possible multimodal mechanism of action. Unlike emetine, dehydroemetine does not significantly inhibit the hERG potassium channel, which is associated with reduced cardiovascular toxicity. The compound's in vitro activity against various parasitic organisms has been characterized using standard antiprotozoal assays, where parasite growth inhibition is measured and IC₅₀ values are determined. Its reduced toxicity compared to emetine makes it a more favorable compound for in vitro and in vivo studies. |
| ln Vivo |
The preparation and physico-chemical characterization of lyophilized polyisohexylcyanoacrylate nanoparticles loaded with dehydroemetine (DHE) for the treatment of visceral leishmaniasis disease is described. The resulting formulation was found to efficiently absorb DHE and gave very reproducible preparations with regard to the size and drug adsorption rate. Stability has been confirmed for at least 24 months. The acute toxicity of DHE was reduced in intravenous administration by its association with nanoparticles. Data concerning tissue distribution in mice showed that DHE nanoparticles were rapidly cleared from the blood stream and that they mainly concentrated in the reticuloendothelial system. Furthermore, DHE linkage to the carrier reduced the cardiac concentrations of the drug[1].
In vivo, dehydroemetine has been used clinically to prevent and treat amoeba infections and diseases. It was developed as a safer alternative to emetine, with reduced cardiovascular toxicity while maintaining similar antiprotozoal efficacy. The compound has been investigated for its effects on cardiac function, with studies examining its impact on spontaneously contracting and electrically driven atrial preparations. Dehydroemetine has also been explored for potential repositioned use in malaria, indicating ongoing interest in its therapeutic applications. Its in vivo efficacy against Entamoeba histolytica infections has been demonstrated in clinical settings, where it has been used as an anti-amoebic agent. The compound's reduced toxicity profile compared to emetine has made it a preferred choice for certain clinical applications. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for dehydroemetine are not as extensively characterized as for many other compounds, as its primary mechanism involves protein synthesis inhibition rather than direct enzyme or receptor binding. However, studies have investigated its effects on cardiac ion channels, particularly the hERG potassium channel, using patch-clamp electrophysiology. Dehydroemetine has been shown to lack significant inhibition of the hERG channel, which is associated with reduced cardiovascular toxicity. Additionally, the compound's effects on mitochondrial membrane potential can be assessed using fluorescent dyes such as JC-1 or tetramethylrhodamine methyl ester (TMRM) in isolated mitochondria or cell-based systems. These assays provide insights into the compound's mechanism of action and potential off-target effects.
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| Cell Assay |
In vitro cell-based assays for dehydroemetine evaluate its antiprotozoal activity and cytotoxicity. For antiprotozoal activity, Entamoeba histolytica cultures or other parasitic organisms are treated with varying concentrations of dehydroemetine, and parasite growth is assessed by counting viable organisms or measuring metabolic activity. IC₅₀ values are determined from dose-response curves. For cytotoxicity assessment, mammalian cell lines are treated with the compound, and cell viability is measured using MTT or other standard assays. The compound's effects on mitochondrial membrane potential can be assessed in cell-based systems using fluorescent dyes. These assays are essential for characterizing the compound's selectivity and therapeutic index.
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| Animal Protocol |
In vivo animal studies for dehydroemetine have been conducted to evaluate its antiprotozoal efficacy and cardiovascular safety. For efficacy studies, animal models of amoebiasis or other parasitic infections are used, where animals are infected with the parasite and treated with dehydroemetine. Endpoints include parasite burden, survival, and clinical signs of infection. For cardiovascular safety studies, the compound's effects on cardiac function have been investigated using isolated atrial preparations from guinea pigs, where the effects on contractility and electrophysiology are measured. These studies have contributed to understanding the compound's reduced cardiotoxicity compared to emetine. Dehydroemetine has also been investigated in models of malaria for potential repositioned use.
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| ADME/Pharmacokinetics |
Dehydroemetine has a molecular weight of approximately 312.36 g/mol. As a pyridoisoquinoline alkaloid, it is a small molecule with drug-like properties. Detailed pharmacokinetic parameters such as absorption, distribution, metabolism, and excretion are not extensively reported in the publicly available literature. The compound is typically administered orally or parenterally for antiprotozoal therapy. Its reduced cardiotoxicity compared to emetine is attributed to its lack of significant hERG channel inhibition. The compound's metabolism and elimination pathways would be similar to other isoquinoline alkaloids, involving hepatic metabolism and renal excretion. Further pharmacokinetic characterization would be necessary for optimal dosing in clinical applications.
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| Toxicity/Toxicokinetics |
Dehydroemetine was developed to address the cardiovascular toxicity associated with emetine. It has reduced cardiotoxicity, attributed to its lack of significant hERG potassium channel inhibition. The compound has been used clinically as an antiprotozoal agent for amoeba infections and diseases. Compared to emetine, dehydroemetine has a similar mechanism of action—inhibiting protein synthesis in Entamoeba histolytica—but with a more favorable safety profile. The compound has also been investigated for potential repositioned use in malaria. It is currently classified as a research-grade compound and is not widely available for clinical use. It has not received FDA approval for any indication.
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| References | |
| Additional Infomation |
Dehydroemetine is a pyridoisoquinoline compound developed to address the cardiovascular toxicity associated with emetine. It is a product of the dehydrogenation of the heterocyclic tricyclic methyl ester of emetine. It is an antimicrobial drug with antimalarial, anti-amoebic, and anti-leishmaniatic activities. It can be used as an antimicrobial drug, an antimalarial drug, and an anti-leishmaniatic drug. It belongs to the isoquinoline, aromatic ether, and pyridoisoquinoline class of compounds. It is derived from the hydride of emetine. Dehydroemetine is a synthetic derivative of emetine used to treat intestinal amebiasis.
Dehydroemetine (CAS# 4914-30-1) is a pyridoisoquinoline alkaloid developed as a safer alternative to emetine for the treatment of amoeba infections. It inhibits protein synthesis in Entamoeba histolytica, disrupting parasite growth. The compound has reduced cardiovascular toxicity compared to emetine, attributed to its lack of significant hERG channel inhibition. Dehydroemetine has been used clinically for amoebiasis and investigated for repositioned use in malaria. It affects mitochondrial membrane potential, suggesting a multimodal mechanism. The compound has not received FDA approval for any indication and is primarily a research-grade compound. |
| Molecular Formula |
C29H38N2O4
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|---|---|
| Molecular Weight |
478.63
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| Exact Mass |
478.283
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| Elemental Analysis |
C, 72.77; H, 8.00; N, 5.85; O, 13.37
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| CAS # |
4914-30-1
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| PubChem CID |
21022
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.19g/cm3
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| Boiling Point |
604.7ºC at 760mmHg
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| Melting Point |
94-96°
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| Flash Point |
319.5ºC
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| Index of Refraction |
1.606
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| LogP |
5.274
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
35
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| Complexity |
744
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CCC1=C(C[C@H]2C3=CC(=C(C=C3CCN2C1)OC)OC)C[C@@H]4C5=CC(=C(C=C5CCN4)OC)OC
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| InChi Key |
XXLZPUYGHQWHRN-RPBOFIJWSA-N
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| InChi Code |
InChI=1S/C29H38N2O4/c1-6-18-17-31-10-8-20-14-27(33-3)29(35-5)16-23(20)25(31)12-21(18)11-24-22-15-28(34-4)26(32-2)13-19(22)7-9-30-24/h13-16,24-25,30H,6-12,17H2,1-5H3/t24-,25+/m1/s1
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| Chemical Name |
(11bS)-2-[[(1R)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl]methyl]-3-ethyl-9,10-dimethoxy-4,6,7,11b-tetrahydro-1H-benzo[a]quinolizine
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| Synonyms |
BT-436; BT 436; Dehydroemetine; 4914-30-1; Mebadin; 2-Dehydroemetine; Dehidroemetina; Dehydroemetinum; (-)-2,3-Dehydroemetine; BT 436; Dehydroemetine
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~104.47 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.22 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.22 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0893 mL | 10.4465 mL | 20.8930 mL | |
| 5 mM | 0.4179 mL | 2.0893 mL | 4.1786 mL | |
| 10 mM | 0.2089 mL | 1.0446 mL | 2.0893 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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