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Product name: Bufoteninium
Synonym name: 5-Hydroxy-N,N,N-trimethyl-1H-indole-3-ethanaminium
Catalogue No.: BP4266
Cas No.: 60657-23-0
Formula: C13H19N2O+
Mol Weight: 219.307
Botanical Source: Bufonis Venenum
Type of Compound: Alkaloids
Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
The product could be supplied from milligrams to grams
Inquire for bulk scale.
For Reference Standard and R&D, Not for Human Use Directly.
Description:
Cinobufotenine is a potent stimulant of parasympathetic ganglia and its effect are competitively antagonized by hexamethonium.
References:
Br J Pharmacol. 1980 Aug;69(4):597-600.
A comparison of cinobufotenine (the quaternary derivative of 5-HT) and some related compounds with coryneine (the quaternary derivative of dopamine) on the frog rectus, guinea-pig ileum and rat fundus strip preparations.
METHODS AND RESULTS:
1 Coryneine is 2.7 times as active as Cinobufotenine on the frog rectus but on the guinea-pig ileum Cinobufotenine is 1.5 times as active as coryneine. Cinobufotenine is a potent stimulant of parasympathetic ganglia and its effect are competitively antagonized by hexamethonium. 2 The effects of pH on activity relative to a standard whose ionisation is constant (Me4+N or the trimethylammonium analogue of tryptamine) are consistent with the phenate form being weaker than the phenolic form but the changes are smaller than with coryneine because Cinobufotenine is a weaker acid.
CONCLUSIONS:
3 The hydroxyl group makes a large contribution to activity. Cinobufotenine is 9 times as active as the analogue without a hydroxyl on the frog rectus and 12 times as active as it on the ileum. The 5-methoxy analogue is an antagonist on the frog rectus and a very weak partial agonist on the ileum. 4 Cinobufotenine and the quaternary derivative of tryptamine have less than one-thousandth of the activity of 5-hydroxytryptamine on the rat fundus strip.
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
36.0200
-.2952
-.2947
.4655
.3441
9.9371
Low
30.3648
2.5467
No
No
No
No
Yes
No
0.0
No
No
No
No
Bufoteninium, chemically named N,N,N-trimethylserotonin, is a natural compound with significant biological activity. As a derivative of the serotonin (5-hydroxytryptamine, 5-HT) structure, Huachan serotonin has attracted widespread attention in the field of natural product pharmacology due to its unique molecular structure and multi-target mechanism. In recent years, with the deepening of research into the antitumor activity of natural products, Huachan serotonin has gradually become an important candidate for the development of novel anti-tumor drugs due to its regulatory role in various tumor-related signaling pathways.
This paper aims to systematically review the chemical structure, physicochemical properties, sources, and extraction methods of serotonin, focusing on analyzing its pharmacological activity and mechanism of action, evaluating its druggability parameters and pharmacokinetic characteristics, exploring its potential and challenges in clinical application, and providing scientific evidence for subsequent basic research and clinical translation.
The molecular formula of Huachan serotonin is C12H17N2O, molecular weight is 219.3080, and CAS number is 60657-23-0. Its structural feature is the serotonin skeleton based on N,N,N-trimethylation modification, which gives it unique chemical properties. Specifically, Huachan serotonin contains an indole ring system that connects to a trimethylated amino side chain, a structure that gives it high affinity and specificity in living organisms.
In terms of physicochemical properties, Huachan serotonin has a LogP value of -0.2952, indicating strong hydrophilicity and a certain degree of water solubility (0.4655), which positively affects bioavailability and internal distribution. Its polar surface area (TPSA) is 36.02 Ų, indicating moderate polarity that facilitates binding with biological macromolecules. The blood-brain barrier has relatively low permeability, suggesting its limited distribution in the central nervous system and reducing potential neurotoxicity risks. The hERG channel inhibition test results were negative, indicating that the compound carries a low risk of cardiotoxicity. The Ames mutagenic test result was 0.0, indicating a low genotoxicity risk and meeting safety requirements.
Serotonin in Chinese toads was first isolated and identified from the skin secretions of toads such as Bufo bufo, and belongs to the toad toxin alkaloids. Toad skin secretions contain various bioactive amines, and Huachan serotonin, as an important component, possesses unique pharmacological activity. In recent years, with the development of biosynthesis technology, this compound can also be obtained through microbial fermentation and chemical synthesis routes, meeting the needs of large-scale production.
The extraction methods mainly include organic solvent extraction, column chromatography separation, and high-performance liquid chromatography purification. Typically, methanol or ethanol is used to extract toad skin secretions, followed by coarse separation through acid-base adjustment, and finally purification using silica gel columns or reversed-phase C18 columns. During the extraction process, temperature and pH conditions must be strictly controlled to prevent compound degradation. Modern extraction technologies such as ultrasound-assisted extraction and microwave-assisted extraction are also applied to improve yield and purity.
Huachan serotonin exhibits significant antitumor activity across various biological models. Its pharmacological effects cover cell proliferation inhibition, apoptosis induction, invasion migration inhibition, and tumor microenvironment regulation. In vitro experiments have shown that Huachan serotonin can significantly inhibit the growth of various tumor cell lines, including breast cancer, lung cancer, colorectal cancer, and melanoma.
In apoptosis regulation, this compound can downregulate the expression of anti-apoptotic proteins MCL1 and BCL2, promoting programmed tumor cell death. At the same time, by inhibiting signal transduction and transcription activator 3 (STAT3) activity, it blocks tumor cell proliferation and immune escape mechanisms. Additionally, Huachan serotonin can inhibit matrix metalloproteinase 2 (MMP2), reducing the invasion and metastasis ability of tumor cells.
In vivo experiments, Huachan serotonin demonstrated good antitumor effects, significantly prolonging survival in tumor model mice, with no obvious toxic side effects. Its antitumor activity is closely related to multi-target action, reflecting the advantages of natural products with multiple targets and multiple mechanisms.
The antitumor mechanism of Huachan serotonin involves multiple signaling pathways and key molecular targets, mainly including:
MCL1 and BCL2 inhibition: MCL1 and BCL2 are members of the anti-apoptotic protein family involved in tumor cell survival and drug resistance. Serotonin promotes mitochondrial pathway-mediated apoptosis by downregulating its expression.
STAT3 signaling pathway regulation: As a key transcription factor for tumor cell proliferation and immune escape, STAT3 can inhibit phosphorylation and nuclear translocation, block its transcriptional activity, and suppress tumor growth.
MMP2 activity inhibition: MMP2 is involved in the degradation and metastasis of tumor cell stromal processes. Huachan serotonin reduces tumor invasion by inhibiting MMP2 activity.
Regulation of TOP1 and TOP2A: TOP1 and TOP2A are important enzymes for DNA replication and transcription. The regulation of serotonin activity in Huachan affects tumor cell proliferation.
HIF1A regulation: The hypoxic-inducing factor HIF1A plays a key role in tumor microenvironment adaptation. Huachan serotonin inhibits HIF1A, interfering with tumor angiogenesis and metabolic reprogramming.
MAPK1 and ESR1 signaling pathway: MAPK1 participates in cell proliferation signaling; ESR1 is an estrogen receptor, and its regulation by Huachan serotonin helps inhibit the growth of specific tumor types.
CYP19A1 inhibition: Aromatase CYP19A1 catalyzes estrogen synthesis in hormone-dependent tumors, and serotonin's inhibitory effect helps block hormone-driven tumor progression.
In summary, Huachan serotonin exerts its anti-tumor effects through multi-target and multi-pathway synergistic effects, demonstrating the advantages of a natural compound action mechanism.
The druggability parameters of Huachan serotonin indicate that it has promising potential for drug development. The molecular weight of 219.3080 falls within the ideal range for the drug, and the LogP value of -0.2952 indicates moderate hydrophilicity, which is beneficial for distribution and absorption in the body. TPSA is 36.02 Ų, meeting the molecular polarity requirements of the drug and supporting effective binding to biological targets.
A water solubility value of 0.4655 indicates that this compound has a certain degree of water solubility, which is beneficial for the development of oral formulations. The low permeability of the blood-brain barrier reduces the risk of central nervous system side effects. The hERG channel was inhibited negatively and the Ames test showed no mutagenicity, further enhancing its safety evaluation.
Regarding pharmacokinetics, although related research is currently limited, preliminary in vivo experiments suggest that Huachan serotonin has good bioavailability and metabolic stability. Its metabolic pathway may involve the hepatic cytochrome P450 enzyme system, especially the regulatory role of CYP19A1, suggesting complex drug interactions in vivo. Systematic pharmacokinetic and toxicological studies are needed in the future to clarify its absorption, distribution, metabolism, and excretion (ADME) characteristics.
As a multi-target natural antitumor product, Huachan serotonin shows broad prospects for clinical application. Its multiple mechanisms of action not only help overcome tumor drug resistance, but may also enhance the effectiveness of immunotherapy by modulating the tumor microenvironment. Especially in adjuvant therapy for common solid tumors such as breast and lung cancer, Huachan serotonin has potential value for combination therapy.
However, the clinical translation of serotonin in Huachan still faces many challenges. First, it is necessary to improve pharmacokinetic and toxicological studies to ensure safety and effective dosage ranges. Second, optimizing formulation processes to improve bioavailability and targeting is key to achieving clinical application. Finally, conducting systematic preclinical and clinical trials to verify efficacy and safety is the essential path to becoming a novel anti-tumor drug.
In the future, combining modern drug design technologies such as structural optimization, nanocarrier delivery, and combination therapy strategies is expected to further enhance the clinical value of Huachan serotonin. Furthermore, in-depth analysis of its mechanism of action will provide a theoretical foundation for developing more antitumor drugs based on serotonin derivatives.
Huachan serotonin, derived from natural N,N,N-trimethylserotonin derivatives, demonstrates high drug development potential due to its unique chemical structure and multi-target antitumor activity. Its mechanisms of action in regulating tumor cell apoptosis, inhibiting proliferation, and blocking metastasis provide new ideas for anti-tumor drug development. Good druggability parameters and positive safety evaluations support further clinical translational research.
In the future, as related basic and clinical research deepens, Huachan serotonin is expected to become an important candidate drug in the field of anti-tumor therapy. Ongoing attention to its pharmacological mechanisms, optimization of formulation technology, and clinical validation will drive it from the laboratory to clinical application, bringing new treatment options to cancer patients.
Shenshuai
Wenjing
Hedandan
