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| Targets |
The biological activity of Quassin is mediated through its interaction with multiple molecular targets and signaling pathways. Its primary mechanism in exerting anti-plasmodial effects involves the inhibition of Plasmodium falciparum, with a notable IC50 of 0.15 μM. In the context of its anti-fertility and anti-estrogenic activities, Quassin is believed to act via the inhibition of estrogen secretion. In vivo studies have demonstrated that treatment with Quassin leads to a significant reduction in serum estrogen levels, which in turn affects reproductive organ weights and litter sizes in animal models. This suggests a direct or indirect modulation of the estrogen receptor signaling pathway, although the precise binding interactions remain to be fully characterized. Furthermore, Quassin has been shown to inhibit both the basal and luteinizing hormone (LH)-stimulated testosterone secretion in rat Leydig cells in a dose-dependent manner, indicating an effect on the hypothalamic-pituitary-gonadal axis. Beyond its endocrine effects, Quassin also modulates immune responses. It has been reported to alter the immunological patterns of murine macrophages through the generation of nitric oxide (NO), exerting antileishmanial activity. This involves the enhancement of NO generation and the upregulation of inducible nitric oxide synthase 2 (iNOS2) expression at both protein and mRNA levels, alongside modulation of cytokines such as TNF-alpha and IL-12. The compound's insecticidal and antifeedant activities are attributed to its general toxicity towards pests like the diamondback moth, though the specific receptors involved are less defined. Overall, Quassin's pharmacology is characterized by its polypharmacological nature, targeting endocrine, immune, and infectious disease pathways, making it a compound of significant interest for diverse research applications.
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| ln Vitro |
Rat Leydig cells' basal and luteinizing hormone-stimulated testosterone production is dose-dependently inhibited by quinine (Compound 1; 5–25 ng/mL) [3].
Quassin has demonstrated a range of in vitro activities across various biological systems, confirming its multi-targeted pharmacological profile. The most prominent in vitro activity is its potent inhibition of the malaria parasite Plasmodium falciparum. Studies have shown that Quassin is effective against both chloroquine-sensitive and chloroquine-resistant strains of P. falciparum, with a reported IC50 of 0.15 μM. This indicates a strong anti-plasmodial effect that is not subject to cross-resistance with conventional anti-malarial drugs, highlighting its potential as a lead compound for new therapeutic strategies. In addition to its anti-parasitic activity, Quassin exhibits significant effects on endocrine function in vitro. It has been observed to inhibit testosterone secretion in rat Leydig cells in a dose-dependent manner, affecting both the basal and luteinizing hormone (LH)-stimulated secretion pathways at concentrations ranging from 5 to 25 ng/mL. This suggests a direct impact on steroidogenesis within the testes. Furthermore, Quassin modulates immune cell function in vitro. It has been shown to alter the immunological patterns of murine macrophages by enhancing the generation of nitric oxide (NO). This is achieved through the upregulation of iNOS2 expression at both the protein and mRNA levels, and it is also associated with modulation of key cytokines such as TNF-alpha and IL-12, indicating a shift towards a pro-inflammatory or host-protective immune phenotype. These in vitro findings collectively demonstrate that Quassin is a compound with potent and diverse biological activities, capable of directly inhibiting pathogen growth, modulating critical hormone production, and influencing the functional state of immune cells, which forms the basis for its various proposed therapeutic applications. |
| ln Vivo |
Treatment of female albino rats with quassin (0.1-2.0 mg/kg; oral; daily; for 60 days) resulted in considerable reductions in uterine and ovarian weights. Additionally, it was demonstrated that rats given quassamine had much lower serum estrogen levels. Rats treated with Quassin had significantly smaller litter sizes and lower body weights. Rats' bodies weight, liver, heart, and kidneys are not negatively impacted by quinine [1].
In vivo studies have corroborated the in vitro findings, demonstrating that Quassin possesses significant biological activity in animal models, particularly in the context of endocrine modulation and reproductive function. A key study involved the oral administration of Quassin to female albino rats at doses ranging from 0.1 to 2.0 mg/kg daily for a period of 60 days. The results of this study showed a considerable and dose-dependent reduction in the weights of the ovaries and uterus in treated animals compared to the control group. This was accompanied by a dramatic decrease in serum estrogen levels, confirming the compound's anti-estrogenic activity in a living organism. The anti-fertility effect was further evidenced by significantly smaller litter sizes and reduced body weights of the offspring in the treated rats. Importantly, despite these pronounced effects on the reproductive system, the study reported that Quassin did not negatively impact the body weight, liver, heart, or kidneys of the rats, suggesting a degree of organ-specific toxicity rather than general systemic toxicity. Beyond its anti-fertility effects, the in vivo immunomodulatory potential of Quassin is also suggested by its ability to alter macrophage immunological patterns, which could translate to enhanced host defense mechanisms against infections. These in vivo results are critical as they not only validate the compound's potent anti-estrogenic and anti-fertility properties observed in vitro but also provide essential data on its efficacy, safety profile, and route of administration, paving the way for further preclinical development. |
| Enzyme Assay |
The in vitro enzyme/receptor binding assays for Quassin are typically designed to investigate its interaction with specific molecular targets, particularly those involved in steroidogenesis and immune modulation. For anti-plasmodial activity, the primary assay involves culturing P. falciparum parasites and measuring the inhibition of parasite growth. Parasite cultures are incubated with varying concentrations of Quassin (e.g., starting from 0.06 μg/mL) alongside a positive control like artesunate. After 48-72 hours of incubation, parasite growth inhibition is assessed, and the IC50 value is determined by nonlinear regression analysis. To study its effects on steroidogenesis, a common protocol involves using primary cultures of rat Leydig cells. The cells are isolated and maintained in culture, then treated with Quassin at concentrations ranging from 5 to 25 ng/mL. The effect on both basal and luteinizing hormone (LH)-stimulated testosterone secretion is measured by collecting the culture media and quantifying testosterone levels using a specific immunoassay such as ELISA or RIA. For immunomodulatory studies, murine macrophages are cultured and treated with Quassin. The generation of nitric oxide (NO) is measured by the Griess reaction, which detects the accumulation of nitrite in the culture medium. The expression of iNOS2 and cytokine genes (e.g., TNF-alpha, IL-12) can be assessed using quantitative real-time PCR (qRT-PCR) at the mRNA level and Western blotting at the protein level. These protocols provide a robust framework for characterizing the binding and functional activity of Quassin on its putative targets.
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| Cell Assay |
In vitro cell-based assays for Quassin are crucial for evaluating its cytotoxic, anti-proliferative, and immunomodulatory effects on various cell lines. For anti-plasmodial activity, the primary cell-based assay involves culturing P. falciparum-infected human erythrocytes. Parasite cultures are maintained in RPMI 1640 medium supplemented with human serum. To determine the anti-malarial activity, cultures are incubated with different concentrations of Quassin for 48-72 hours. The percentage of parasitemia is then assessed by microscopic examination of Giemsa-stained blood smears, or by using a fluorescence-based method like SYBR Green I assay, which measures parasite DNA. The IC50 is calculated from dose-response curves. For studying its effects on mammalian cells, such as its anti-endocrine activity, primary cultures of rat Leydig cells are used. The cells are seeded in multi-well plates and treated with Quassin (5-25 ng/mL). Cell viability is typically assessed using an MTT or resazurin assay to ensure that observed effects on testosterone secretion are not due to cytotoxicity. Testosterone levels in the culture supernatant are then quantified using an enzyme-linked immunosorbent assay (ELISA). For immunomodulatory studies, murine macrophage cell lines (e.g., RAW 264.7) or primary peritoneal macrophages are treated with Quassin. Following treatment, the supernatant is collected to measure nitric oxide production via the Griess reaction. The cells are then lysed for RNA or protein extraction to analyze the expression of iNOS2, TNF-α, and IL-12 by qRT-PCR and Western blot, respectively. These assays provide comprehensive data on the compound's bioactivity and its mechanism of action at the cellular level.
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| Animal Protocol |
Animal/Disease Models: 35 female albino rats (150-170 g) [1]
Doses: 0.1 mg/kg, 1.0 mg/kg and 2.0 mg/kg Route of Administration: po (po (oral gavage)) Daily; continued for 60 days Experimental Results: Ovarian and uterine weights diminished Dramatically in all groups compared to the control group. Serum estrogen levels were also Dramatically diminished in quassamine-treated rats. In vivo animal experiments for Quassin are primarily conducted to evaluate its anti-fertility, anti-estrogenic, and potential toxicological effects. A standard protocol utilizes female albino rats, typically weighing between 150-170 grams. In a typical study, the animals are randomly divided into control and treatment groups. The treatment group receives Quassin orally via gavage at various doses, such as 0.1 mg/kg, 1.0 mg/kg, and 2.0 mg/kg, on a daily basis for a prolonged period, often 60 days. The control group receives the vehicle only. During the treatment period, the animals are monitored for general health, body weight changes, and any signs of toxicity. At the end of the experiment, the animals are sacrificed, and key organs such as the ovaries, uterus, liver, heart, and kidneys are carefully dissected and weighed. Blood samples are collected for serum isolation to measure hormone levels, particularly estrogen, using radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA). The litter size and body weights of any offspring are also recorded as a direct measure of fertility. The collected organ weights and serum hormone levels are then statistically compared between the control and treatment groups to determine the compound's efficacy and potential organ-specific toxicity. These experiments are critical for establishing the in vivo pharmacological profile and safety margin of Quassin. |
| ADME/Pharmacokinetics |
The pharmacokinetic (PK) properties of Quassin have not been extensively detailed in the available literature, but some properties can be inferred from its physicochemical characteristics. Quassin has a molecular weight of 388.46 g/mol and a logP value of 2.22, indicating moderate lipophilicity, which generally favors good membrane permeability and oral absorption. Indeed, in vivo studies have successfully administered Quassin via the oral route (per os, p.o.), demonstrating that it is orally bioavailable and can exert significant systemic effects, such as reducing serum estrogen levels and altering reproductive organ weights. Its chemical structure includes multiple oxygen-containing functional groups, which contribute to a high number of hydrogen bond acceptors (6) but no hydrogen bond donors, a factor that can influence its solubility and metabolic stability. The compound is soluble in organic solvents like chloroform, DMSO, and ethyl acetate, which is typical for its extraction and formulation for in vivo studies. For storage, it is recommended to keep Quassin as a powder at -20°C, where it can remain stable for up to three years, indicating good long-term stability. However, comprehensive PK parameters such as half-life (t1/2), volume of distribution (Vd), clearance (Cl), and bioavailability have not been reported. Further studies, including detailed plasma concentration-time profiles after intravenous and oral administration, are necessary to fully characterize its absorption, distribution, metabolism, and excretion (ADME) properties.
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| Toxicity/Toxicokinetics |
The toxicological profile of Quassin, based on available in vivo studies, suggests a degree of organ-specific toxicity rather than generalized systemic toxicity. In a 60-day study where female albino rats were orally administered Quassin at doses of 0.1, 1.0, and 2.0 mg/kg, the compound did not negatively impact the body weight, liver, heart, or kidneys of the treated animals, indicating that these major organs were not adversely affected at the tested doses. This suggests a relatively favorable safety margin concerning vital organ function. However, the same study demonstrated significant toxicity to the reproductive system. Treatment with Quassin resulted in considerable reductions in uterine and ovarian weights and dramatically decreased serum estrogen levels, which correlated with significantly smaller litter sizes. These effects highlight that Quassin has potent anti-estrogenic and anti-fertility activity, which can be considered a form of targeted reproductive toxicity. The compound's reversible brood-repellent activity further supports its effect on reproductive processes. While these studies did not report acute toxicity or mortality at the doses used, the potential for cumulative or long-term toxic effects has not been fully explored. Therefore, although initial findings suggest that Quassin may be well-tolerated by non-reproductive organs, its pronounced effects on endocrine and reproductive function necessitate careful consideration in any potential therapeutic application.
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| References |
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| Additional Infomation |
Quassin is a triterpenoid compound. 2,12-DimethoxyQuassin-2,12-diene-1,11,16-trione has been reported in Melastoma canadensis, Melastoma ferrugineum, and other organisms with relevant data.
Quassin is primarily a research compound and is not approved for any clinical or therapeutic use. It is exclusively utilized as a tool in biochemical and pharmacological research to study the diverse activities of quassinoids. Its significance lies in its role as a lead compound for the development of novel therapeutic agents. The compound's potent and reversible anti-fertility properties have sparked interest in its potential application for population control, particularly in managing pest species or for reproductive health research. Furthermore, its strong anti-plasmodial activity against both chloroquine-sensitive and resistant strains of P. falciparum positions it as a valuable candidate for the development of new anti-malarial drugs, addressing the urgent need for novel treatments due to rising drug resistance. Quassin's immunomodulatory effects, particularly its ability to enhance nitric oxide generation and modulate cytokine expression in macrophages, also make it a useful tool for studying host immune responses and inflammatory pathways. In addition to its biomedical applications, Quassin has been studied for its insecticidal and antifeedant properties against agricultural pests, indicating potential use in crop protection. Its complex chemical structure also makes it a subject of interest in synthetic chemistry for total synthesis and analog development. Overall, Quassin serves as a multifaceted research compound with potential applications spanning drug discovery, immunology, and agriculture. |
| Molecular Formula |
C22H28O6
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| Molecular Weight |
388.46
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| Exact Mass |
388.188
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| CAS # |
76-78-8
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| PubChem CID |
65571
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
586.3±50.0 °C at 760 mmHg
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| Melting Point |
200 - 222ºC
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| Flash Point |
255.4±30.2 °C
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| Vapour Pressure |
0.0±1.6 mmHg at 25°C
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| Index of Refraction |
1.553
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| LogP |
2.22
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
28
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| Complexity |
838
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| Defined Atom Stereocenter Count |
7
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| SMILES |
C[C@@H]1C=C(C(=O)[C@]2([C@H]1C[C@@H]3[C@@]4([C@@H]2C(=O)C(=C([C@@H]4CC(=O)O3)C)OC)C)C)OC
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| InChi Key |
IOSXSVZRTUWBHC-LBTVDEKVSA-N
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| InChi Code |
InChI=1S/C22H28O6/c1-10-7-14(26-5)20(25)22(4)12(10)8-15-21(3)13(9-16(23)28-15)11(2)18(27-6)17(24)19(21)22/h7,10,12-13,15,19H,8-9H2,1-6H3/t10-,12+,13+,15-,19+,21-,22+/m1/s1
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| Chemical Name |
(1S,2S,6S,7S,9R,13R,17S)-4,15-dimethoxy-2,6,14,17-tetramethyl-10-oxatetracyclo[7.7.1.02,7.013,17]heptadeca-4,14-diene-3,11,16-trione
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| Synonyms |
(+)-QuassinQuassin
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5743 mL | 12.8713 mL | 25.7427 mL | |
| 5 mM | 0.5149 mL | 2.5743 mL | 5.1485 mL | |
| 10 mM | 0.2574 mL | 1.2871 mL | 2.5743 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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