Product name: Bufotalidin
Synonym name:
Catalogue No.: BP4193
Cas No.: 465-90-7
Formula: C₂₄H₃₂O₆
Mol Weight: 416.514
Botanical Source: Bufonis Venenum
Type of Compound: Steroids

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.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.

The product could be supplied from milligrams to grams
Inquire for bulk scale.

For Reference Standard and R&D, Not for Human Use Directly.

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Bufotalidin, CAS number 465-90-7, is a steroidal aldehyde natural compound derived from toad secretions, belonging to the 5β-bufanolide family. As a typical class of toad toxins, toad taridine has attracted widespread attention in the field of natural product pharmacology in recent years due to its unique chemical structure and diverse biological activities. It not only exhibits significant anti-tumor, anti-leishmaniasis, and autophagy-inducing activities, but also plays an important role in regulating apoptosis and metabolism. This paper aims to systematically review the chemical structure, origin, pharmacological activity, mechanism of action, and druggability evaluation of Toad Taridine, exploring its potential and challenges in future clinical applications.

Chemical structure and physicochemical properties

Toad Talidin is a steroid aldehyde with a complex structure, molecular formula C_24H_34O_6, and molecular weight 416.5140. Its structural features include various functional groups such as 3β-hydroxy, 14β-hydroxyl, 19-oxo, and 5β-hydroxyl, making it a mixed compound of steroid aldehydes and sterolide. This compound has moderate lipid solubility, with a LogP value of 1.6836, indicating good lipid solubility that facilitates cell membrane penetration. The polar surface area (TPSA) was 107.97 Ų, indicating certain polar characteristics in drug absorption and distribution.

Toad Talidin has relatively low water solubility (0.0243 mg/mL), which somewhat limits its bioavailability, but its high blood-brain barrier penetration ability offers potential for treating central nervous system diseases. Notably, this compound showed negative results in hERG channel inhibition experiments, indicating a low risk of cardiotoxicity; At the same time, Ames' mutagenicity test result was zero, indicating a low genotoxicity risk.

Plant Origins and Extraction Methods

Toad Talidin is mainly found in the secretions of skin glands of toads (Bufo spp.) and is one of the important defensive alkaloids in the toad. Its natural sources mainly include the Chinese toad (Bufo gargarizans) and the American toad (Bufo marinus). In traditional Chinese medicine, toad secretions are used as topical medicines to treat tumors and inflammatory diseases, while modern research has isolated active ingredients such as toad taridin.

The extraction method typically uses organic solvent extraction combined liquid-liquid distribution technology. The general steps include: collecting and drying toad secretions, followed by extraction with methanol or ethanol, concentration and distribution through ethyl acetate-water systems, followed by purification using silica gel column chromatography or high-performance liquid chromatography (HPLC). In recent years, supercritical CO_2 extraction technology has also been applied to improve extraction efficiency and purity, reduce the use of organic solvents, and align with the concept of green chemistry.

Pharmacological activity research

Toad Taridin has rich pharmacological activities, covering anti-tumor, autophagy induction, apoptosis regulation, and antiparasitic properties.

Antitumor activity

Toad Taridin exhibited significant cell proliferation inhibition in various tumor cell lines. In vitro experiments have shown that it can significantly reduce cancer cell survival rates by inducing cell cycle arrest and promoting apoptosis. The research covers a variety of solid tumor types, including breast, lung, liver, and colorectal cancer. Its antitumor activity is related to regulating multiple signaling pathways, such as inhibiting STAT3 and MAPK1 signaling, reducing MMP2-mediated cell migration capacity, and suppressing tumor metastasis potential.

Autophagy induction and apoptosis

Toads can definitely activate cellular autophagy by regulating the expression of autophagy-related proteins LC3 and Beclin-1, thereby promoting the formation of autophagosomes. Additionally, its induced apoptosis manifests as loss of mitochondrial membrane potential, activation of Caspase cascade reactions, and changes in the expression of BCL2 family proteins, demonstrating its multiple roles in regulating cell fate.

Activity against leishmaniasis

As a natural antiparasitic, Toad Taridine shows good inhibitory effects against Leishmania. Its mechanism of action may involve damaging the integrity of parasitic cell membranes and interfering with parasitic energy metabolism, offering potential for the development of novel antiparasitic drugs.

Other pharmacological effects

Toad Taridine has also been found to regulate animal metabolism, possibly by influencing steroid-metabolizing enzyme activity, thereby modulating endocrine and metabolic balance. Additionally, it has been reported to participate in defense responses in plant metabolism, demonstrating the diversity of its biological functions.

Mechanism of action and molecular targets

The pharmacological effects of toad taridine depend on its interactions with various molecular targets, especially in the antitumor field.

• MCL1 and BCL2: As anti-apoptotic proteins, MCL1 and BCL2 play key roles in cancer cell survival. Toad Taridin promotes mitochondria-mediated activation of apoptotic pathways by downregulating the expression of these two proteins.
• STAT3: The STAT3 signaling pathway plays a central role in tumor cell proliferation, immune evasion, and metastasis. Toad Taridin inhibits STAT3 phosphorylation, blocks its transcriptional activity, and suppresses tumor progression.
• MMP2: Matrix metalloproteinase 2 participates in the degradation of the extracellular tumor matrix, promoting invasion and metastasis. Toad Taridine inhibits MMP2 expression and restricts tumor cell migration.
• TOP1 and TOP2A: Topoisomerases 1 and 2A are enzymes essential for DNA replication and transcription. Toad Taridine may interfere with their function and block DNA synthesis in cancer cells.
• HIF1A: Hypoxia-inducing factor 1α regulates tumor hypoxia adaptation; Toad Talidine reduces tumor drug resistance and angiogenesis by inhibiting HIF1A.
• MAPK1: As a key member of the MAPK signaling pathway, MAPK1 regulates cell proliferation and differentiation. Toads achieve anti-tumor effects by modulating this pathway.
• ESR1 and CYP19A1: Estrogen receptor α (ESR1) and aromatase (CYP19A1) play significant roles in hormone-dependent tumors, and Toad Taridine may exert antitumor effects by modulating hormone signaling pathways.

In summary, Toad Taridine demonstrates a complex yet effective pharmacological mechanism through multi-target and multi-pathway synergistic effects.

Druggability evaluation and pharmacokinetics

The druggability evaluation of Toad Ta Li Ding indicates that it has certain potential for drug development. Its molecular weight of 416.5 meets the requirements of Lipinski's rules, and a moderate LogP value suggests good membrane permeability. A higher TPSA value may limit oral absorption, but its advanced blood-brain barrier penetration provides advantages for treating central nervous system-related diseases.

Low water solubility is a major limitation for drug development, requiring improved bioavailability through pharmaceutical formulation technology. In vivo pharmacokinetic studies are still incomplete, but preliminary data indicate that it is widely distributed in animals, has stable metabolism, and does not exhibit significant cardiotoxicity risk.

The hERG channel inhibition test was negative, reducing the risk of arrhythmias; The Ames mutagenic test yielded no positive results, indicating good genetic safety. These data provide strong support for its preclinical safety evaluation.

Future research should focus on its in vivo metabolic pathways, half-life, and drug interactions to refine its pharmacokinetic characteristics and guide clinical development.

Prospects and outlooks for clinical applications

Toad Talidine, as a multifunctional natural steroid aldehyde, has broad pharmacological activity and shows promising application prospects especially in the anti-tumor field. Its multi-target mechanism of action gives it unique advantages in overcoming tumor resistance, inhibiting metastasis, and inducing apoptosis. High blood-brain barrier penetration capability makes treatment possible for central nervous system diseases such as brain tumors.

However, the low water solubility and potential toxicity risks of toad Taridin remain major obstacles to clinical translation. In the future, modern drug delivery technologies such as structural modification and nanocarriers will be needed to enhance bioavailability and targeting, thereby reducing side effects.

Moreover, the potential of Toad Taridin in antiparasitic and metabolic regulation remains to be explored further. By integrating modern molecular biology techniques and systematically analyzing its network of effects, it is expected to promote its multi-field clinical application.

Overall, Toad Taridine, as a typical representative of natural product drug development, has the potential to become a novel antitumor and antiparasitic drug. Future research should focus on optimizing its efficacy and safety evaluation to promote its clinical translation.

Conclusion

Toad Taridine, as a unique natural steroid aldehyde product, has become an important subject of natural product pharmacological research due to its diverse biological activities and complex mechanisms of action. This paper systematically reviews its chemical structure, origin, pharmacological activity, mechanism of action, and druggability evaluation, revealing its potential in anti-tumor, autophagy induction, and antiparasitic properties. Despite challenges such as poor water solubility and insufficient safety evaluation, Toad Taridine still demonstrates promising clinical application prospects. In the future, through multidisciplinary collaboration, optimizing drug properties and delivery systems is expected to enable the transformation from natural products to clinical drugs, benefiting patients.