Product name: Yadanziolide B
Synonym name:
Catalogue No.: BP4227
Cas No.: 95258-13-2
Formula: C₂₀H₂₆O₁₁
Mol Weight: 442.417
Botanical Source: Brucea javanica（L.）Merr.
Type of Compound: Diterpenoids

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.

HPLC of Yadanziolide B

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

Introduction/Overview

Yadanziolide B (CAS No.: 95258-13-2) is a natural quassi-lignan compound derived from plants of the Picrasma quassioides. Due to its unique chemical structure and diverse biological activities, it has attracted widespread attention in the field of natural product pharmacology in recent years. As a δ-lactone secondary α-hydroxyketone compound, Jalanolide B not only exhibits significant antitumor activity but has also been found to have potential H5N1 neuraminidase inhibitory effects, indicating its potential application in the field of antiviral therapy. Its complex molecular structure endows it with multi-target regulatory capabilities, involving several key biological pathways such as apoptosis, signal transduction, and metabolic regulation.

This paper aims to systematically review the chemical structure and physicochemical properties of Javenolide B, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and pharmacokinetic characteristics, as well as explore its clinical application prospects and future research directions, providing theoretical basis and research references for drug development of this natural product.

Chemical structure and physicochemical properties

Javenolide B belongs to the quasticin class of compounds, with a chemical structure based on the 13,20-epoxypicras-3-ene framework, molecular formula C_24H_34O_8, and molecular weight 442.4170. Its structural features include substitutions at positions 1, 6, 11, 12, 14, 15, and 21, and oxygen substitutions at positions 2 and 16, forming multiple hydroxyl and ketone groups, which impart high polarity and rich chemical reactivity. This compound contains a δ-lactone ring structure and belongs to the α-hydroxyketone class of organic heteropentacyclic compounds, and it also contains functional groups such as enone and heptanol.

In terms of physicochemical properties, the LogP value of Javanolide B is -1.3914, indicating strong hydrophilicity, and the TPSA (topological pole surface area) is 194.2100, indicating that its molecules have high polarity and the number of hydrogen bond donors/acceptors, which may affect its cell membrane penetration ability. Water solubility is 8.5499, indicating good solubility in the aqueous phase, which is beneficial for absorption and distribution in the body. The blood-brain barrier permeability was low, hERG channel inhibition tests were negative, and Ames-related mutagenicity tests were zero, indicating high safety and low potential cardiotoxicity risk.

Plant Origins and Extraction Methods

Javenolide B is mainly isolated from the ethanol extract of the stems of Picrasma quassioides. Plants of the Picrasma quassioides are widely distributed in tropical and subtropical regions of Asia, and in traditional Chinese medicine, their roots, stems, leaves, and other parts are often used to treat various diseases. During extraction, 70%-95% ethanol is typically used as the solvent, and plant active ingredients are extracted by reflux extraction or ultrasound-assisted extraction methods. The extract is concentrated, separated, column chromatography (such as silica gel columns, reversed-phase C18 columns), and purified by high-performance liquid chromatography (HPLC) to obtain high-purity jabolide B.

Optimizing the extraction process includes adjusting parameters such as solvent selection, extraction time, temperature, and extraction frequency to improve yield and purity. Moreover, the application of modern separation technologies such as preparative HPLC and countercurrent chromatography has promoted efficient separation and purification of this compound.

Pharmacological activity research

Research on the pharmacological activity of Javanolide B mainly focuses on antitumor and antiviral properties. Multiple in vitro cell experiments have shown that this compound has significant cytotoxic effects on various tumor cell lines, inducing tumor cell apoptosis and inhibiting cell proliferation and migration. Additionally, crowulide B exhibited inhibitory activity against neuraminidase of the H5N1 influenza virus, suggesting its potential as an antiviral drug candidate.

Antitumor activity

Javanolide B exerts its antitumor effect through multi-target regulation. It inhibits anti-apoptotic proteins such as MCL1 and BCL2, promoting cancer cell apoptosis; By inhibiting the STAT3 signaling pathway, it blocks tumor cell proliferation and immune evasion; At the same time, it inhibits MMP2 expression to reduce tumor cell invasion and metastasis. The inhibitory effects of TOP1 and TOP2A interfere with DNA replication and transcription, blocking the tumor cell cycle progression. Regulation of HIF1A helps inhibit adaptation to the tumor hypoxic microenvironment and reduces tumor drug resistance. Regulation of the MAPK1 pathway further affects the balance of cell proliferation and apoptosis. The effects of Javanolide B on ESR1 and CYP19A1 suggest its potential therapeutic value in hormone-dependent tumors such as breast cancer.

Antiviral activity

As an H5N1 neuraminidase inhibitor, Jadanolide B can block viral release and transmission, inhibiting viral replication. Although current related research is relatively preliminary, its unique structure provides important clues for designing novel anti-influenza drugs.

Mechanism of action and molecular targets

The multi-target mechanism of Javanolide B reflects its complex molecular regulatory network. By directly or indirectly acting on various protein targets, it regulates intracellular signaling pathways and exerts its biological functions.

1. MCL1 and BCL2 regulate apoptosis
   MCL1 and BCL2 are members of the anti-apoptotic protein family. Javanolide B promotes mitochondrial pathway-mediated apoptosis by inhibiting its expression or function, inducing programmed tumor cell death.

2. STAT3 signaling pathway inhibition
   STAT3 plays a central role in tumor cell proliferation, survival, and immune regulation. Javanolide B inhibits STAT3 phosphorylation and inhibits its transcriptional activity, thereby reducing the malignant phenotype of tumor cells.

3. MMP2 inhibits tumor invasion
   MMP2 participates in extracellular matrix degradation and promotes tumor cell migration. Javenolide B inhibits MMP2 expression and reduces tumor metastatic potential.

4. TOP1 and TOP2A interfere with DNA metabolism
   Topoisomerases I and II are key enzymes for DNA replication and transcription. Javanolide B inhibits its activity, leading to DNA damage accumulation and blocking the cell cycle progression.

5. HIF1A regulates the tumor microenvironment
   HIF1A is activated under tumor hypoxia, promoting angiogenesis and metabolic reprogramming. Javenolide B weakens tumor adaptability and resistance by inhibiting HIF1A.

6. MAPK1 signal regulation
   MAPK1 is involved in cell proliferation and stress responses. Javanolide B regulates MAPK1 activity and influences cell fate decisions.

7. ESR1 and CYP19A1 regulate endocrine signals
   ESR1 is an estrogen receptor and CYP19A1 an aromatase; both are key in hormone-dependent tumors. Javanolide B regulates it, suggesting its potential for application in diseases such as breast cancer.

Druggability evaluation and pharmacokinetics

The druggability evaluation of Javanolide B indicates that it has certain potential for drug development. Its molecular weight is moderate (442.4170), and although LogP is negative, indicating high hydrophilicity, a larger TPSA (194.2100) may limit its cell membrane penetration and oral bioavailability. It has good water solubility, which is beneficial for distribution and excretion in the body.

The low permeability of the blood-brain barrier suggests it is difficult to enter the central nervous system, reducing neurotoxicity risks but also limiting its application in neurological diseases. hERG channel inhibition is negative, indicating a low risk of cardiotoxicity and good safety. The Ames test result was negative, supporting the absence of significant mutagenicity.

Currently, pharmacokinetic data on Javanolide B are limited, and further studies on in vivo absorption, distribution, metabolism, and excretion (ADME) are needed to clarify its half-life, bioavailability, and metabolic pathways, providing a basis for preclinical drug development.

Prospects and outlooks for clinical applications

Javanolide B, with its multi-target antitumor activity and potential antiviral effects, has broad clinical application prospects. For tumor treatment, by regulating key apoptosis and signaling pathways, it may become a candidate molecule for novel anticancer drugs, especially with special advantages in hormone-dependent tumors such as breast cancer. In the field of antiviral infections, the inhibitory activity of neuraminidase against the H5N1 influenza virus offers new ideas for the treatment of influenza virus infections.

Future research should focus on the following aspects:

1. Structural optimization and derivative design
   Chemical modification enhances membrane permeability and oral bioavailability, enhancing efficacy and safety.

2. Pharmacokinetics and toxicology studies of systems
   Clarifying metabolic pathways, potential toxicity, and long-term safety in vivo lays the foundation for clinical translation.

3. In-depth mechanism analysis and multi-target network construction
   Using omics and systems biology methods, we can comprehensively reveal its mechanisms of action and guide precise medication.

4. Preclinical animal model validation
   Evaluate its in vivo antitumor and antiviral effects to verify efficacy and safety.

5. Exploring combination medication strategies
   Explore synergies with existing chemotherapy or antiviral drugs to enhance efficacy and reduce resistance.

Conclusion

Javenolide B, a natural quasticin compound with a unique structure and multiple biological activities, demonstrates outstanding anti-tumor and antiviral potential. Its multi-target mechanism of action provides a valuable example for the development of natural product drugs. Although there are still shortcomings in pharmacokinetics and preclinical research, with deeper research and technological advancements, Javanolide B is expected to become an important candidate for next-generation anti-tumor and antiviral drugs. Future systematic research will provide a solid scientific foundation for its clinical applications and drug development.