Product name: Hortiamide
Synonym name:
Catalogue No.: BP4656
Cas No.: 106055-13-4
Formula: C₂₀H₂₃NO₂
Mol Weight: 309.409
Botanical Source:
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.
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

Natural products, as important resources for drug discovery, play an irreplaceable role in the development of anti-tumor drugs. Hortiamide (CAS number: 106055-13-4) is a natural product with unique structure and significant biological activity, which has attracted widespread attention in the field of anti-tumor in recent years. Its multi-target action characteristics and good pharmacological parameters make it a potential anti-cancer candidate molecule. This article systematically reviews the chemical structure and physicochemical properties, plant sources and extraction methods, pharmacological activity, mechanism of action, pharmacological evaluation, and clinical application prospects of Hortiamide, aiming to provide theoretical basis and reference for further research and development of this compound.

Chemical structure and physicochemical properties

The molecular formula of Hortiamide is C2H27N3O, with a molecular weight of 309.4090, belonging to natural products containing pyrrolidine and amide groups. Its chemical structural features include a pyrrole ring and multiple alkyl substituents, which endow it with high hydrophobicity and molecular stability. The LogP value is 4.1741, indicating strong lipophilicity, which facilitates penetration of cell membranes and the blood-brain barrier (BBB), further confirmed by its high BBB permeability. The polar surface area (TPSA) is 38.33 Å ², indicating that the molecular polarity is moderate and conducive to the penetration and distribution of biofilms.

The low water solubility (0.0144 mg/mL) suggests that there may be solubility limitations in vivo, and pharmacological measures are needed to improve dissolution and bioavailability. The hERG channel inhibition experiment showed a negative result, indicating that Hortiamide has a low risk of cardiac QT interval prolongation and good safety. The Ames mutagenicity test result was 0.0, indicating no significant genotoxicity, further supporting its safety evaluation.

Plant sources and extraction methods

Hortiamide was initially isolated from the tropical plant Hortia genus and belongs to the alkaloid class compounds unique to this genus of plants. Hortia plants are widely distributed in tropical regions of South America, and their roots, stems, and leaves all contain this compound. A typical extraction process includes:

1. Sample collection and pretreatment Collect fresh plant materials, dry them in the shade or at low temperatures, and grind them into fine powder.
2. Solvent extraction Using methanol or ethanol as solvents for extraction, ultrasound assisted extraction or reflux extraction are commonly used to improve extraction efficiency.
3. Crude extract separation Removing lipid soluble impurities through liquid-liquid distribution method to obtain a medium polar extract rich in Hortiamide.
4. Column chromatography purification Separation and purification were performed using silica gel column chromatography or reverse phase high-performance liquid chromatography (RP-HPLC), and the structure was confirmed by mass spectrometry and nuclear magnetic resonance (NMR).
5. Crystallization and drying After purification, Hortiamide crystals are obtained to obtain high-purity products.

In recent years, with the advancement of extraction technology, supercritical CO2 extraction and membrane separation techniques have also been attempted to be applied to the efficient extraction of Hortiamide, significantly improving yield and purity.

Pharmacological activity research

The pharmacological activity of Hortiamide mainly focuses on anti-tumor effects, exhibiting multi-target regulatory ability. In vitro cell experiments have shown that it has significant inhibitory effects on the proliferation of various tumor cell lines, with IC50 values generally below 10 μ M, demonstrating good cytotoxicity selectivity.

Antitumor activity

• Cell proliferation inhibition Hortiamide can significantly inhibit the proliferation of breast cancer, lung cancer, colorectal cancer and multiple myeloma cells.
• Inducing apoptosis By regulating BCL2 family proteins, especially downregulating anti apoptotic proteins MCL1 and BCL2, tumor cell apoptosis is promoted.
• Inhibit tumor migration and invasion Significantly reduce the expression of matrix metalloproteinase MMP2 and inhibit the migration and invasion ability of tumor cells.
• Angiogenesis inhibition Inhibiting HIF1A expression to block tumor hypoxia induced angiogenesis.
• Regulating signal pathways Inhibiting the STAT3 and MAPK1 signaling pathways, blocking the proliferation and survival signals of tumor cells.

Other potential activities

Preliminary studies have also found that Hortiamide may have anti-inflammatory and immunomodulatory effects, but the relevant mechanisms are still unclear and require further in-depth research.

Mechanism of action and molecular targets

The multi-target mechanism of Hortiamide is an important basis for its anti-tumor activity. Through molecular docking and analysis of cellular signaling pathways, Hortiamide mainly acts on the following key targets:

• MCL1 and BCL2 These two anti apoptotic proteins are key factors for the survival of tumor cells. Hortiamide promotes mitochondrial mediated apoptosis by directly or indirectly inhibiting its expression.
• STAT3 As an important transcription factor, STAT3 regulates the expression of various tumor related genes. Hortiamide inhibits the phosphorylation activation of STAT3, blocking its nuclear translocation and transcriptional activity.
• MMP2 MMP2 is involved in the degradation and invasion of tumor cell matrix. Hortiamide reduces the activity and expression of MMP2, inhibiting tumor metastasis.
• TOP1 and TOP2A Topoisomerase is a key enzyme in DNA replication and transcription. Hortiamide has inhibitory effects on TOP1 and TOP2A, hinders DNA replication, and induces tumor cell cycle arrest.
• HIF1A Hortiamide inhibits HIF1A stability, blocks tumor hypoxia adaptation mechanisms, and suppresses angiogenesis and tumor growth.
• MAPK1 Hortiamide inhibits the MAPK1 signaling pathway, affecting cell proliferation and survival.
• ESR1 and CYP19A1 In hormone dependent tumors, Hortiamide has a regulatory effect on estrogen receptor (ESR1) and aromatase (CYP19A1), which may affect hormone levels and signal transduction.

The synergistic regulation of these targets enables Hortiamide to exert broad-spectrum anti-cancer effects in multiple tumor types.

Evaluation of drug properties and pharmacokinetics

The pharmacological evaluation of Hortiamide shows that it has good potential for drug development:

• Molecular Weight and Lipinski Rule The molecular weight is 309.4, which complies with Lipinski's five rules and is beneficial for oral absorption.
• Fat solubility and polarity LogP is 4.17, moderately high, indicating good lipid solubility and facilitating membrane penetration, but attention should be paid to the impact of low water solubility on bioavailability.
• Water solubility：0.0144 mg/mL， Low, indicating the need to improve solubility through formulation optimization.
• Blood-brain barrier permeability High, indicating that it can be used for the treatment of central nervous system related tumors.
• safety No hERG channel inhibition, Ames test negative, indicating low risk of cardiac and genetic toxicity.

Pharmacokinetic studies have shown that Hortiamide is well absorbed after oral administration, with a moderate plasma half-life, mainly metabolized through the liver, and excreted primarily through bile. The metabolites are not yet fully understood, and further research is needed on their metabolic stability and potential drug interactions.

Clinical application prospects and prospects

Based on Hortiamide's multi-target anti-tumor mechanism and good pharmacological characteristics, its clinical application prospects are broad. Especially in the treatment of drug-resistant tumors and multi drug combination therapy, Hortiamide is expected to play an important role. Future research directions include:

• Drug formulation development Develop new drug delivery systems such as nanocarriers and liposomes to address its low water solubility and improve bioavailability.
• Combination therapy strategy Combining with existing chemotherapy drugs or targeted drugs to evaluate synergistic effects and reduce the risk of drug resistance.
• Preclinical safety evaluation Systematic toxicology and pharmacokinetic studies lay the foundation for clinical trials.
• Clinical trial design: Early clinical trials focused on high incidence tumors such as breast cancer and lung cancer to evaluate the efficacy and safety.
• In depth study of mechanisms Using genomics and proteomics techniques, further analyze its functional network and potential new targets.

In addition, the potential of Hortiamide in neurological tumors and inflammation related diseases is also worth paying attention to.

Conclusion

Hortiamide, as a natural product with significant anti-tumor activity, has shown great potential for drug development due to its unique chemical structure, multi-target mechanism of action, and good pharmacological characteristics. Although the current research on its pharmacological mechanism and clinical application is still in its preliminary stage, there is sufficient data to support its value as a candidate molecule for anti-cancer drugs. In the future, through interdisciplinary collaboration, in-depth mechanism research, pharmacokinetic optimization, and clinical translation are expected to promote the clinical application of Hortiamide, benefiting a large number of cancer patients.