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 No.: 106055-13-4) is a natural product with a unique structure and significant bioactivity, and has attracted widespread attention in the field of anti-tumor treatment in recent years. Its multi-target action characteristics and favorable druggability parameters make it a potential anti-cancer candidate molecule. This paper systematically reviews the chemical structure and physicochemical properties of hortiamide, plant origin and extraction methods, pharmacological activity, mechanism of action, druggability evaluation, and clinical application prospects, aiming to provide a theoretical basis and reference for further research and development of this compound.

Chemical structure and physicochemical properties

Hortiamide has the molecular formula C_20H_27N_3O and a molecular weight of 309.4090, making it a natural product containing pyrrolidine and amide groups. Its chemical structure features include a pyrrole ring and multiple alkyl substituents, giving it high hydrophobicity and molecular stability. The LogP value was 4.1741, indicating strong lipid solubility, which facilitates penetration of cell membranes and the blood-brain barrier (BBB), further confirmed by its high BBB permeability. The polar surface area (TPSA) was 38.33 Ų, indicating moderate molecular polarity, which is conducive to biofilm penetration and distribution.

Low water solubility (0.0144 mg/mL) suggests possible solubility limits in vivo, requiring pharmaceutical methods to improve dissolution and bioavailability. The hERG channel inhibition test results were negative, indicating that hortiamide carries a lower risk of cardiac QT interval prolongation and is relatively safe. The Ames mutagenic test result was 0.0, indicating no significant genotoxicity, further supporting its safety evaluation.

Plant Origins and Extraction Methods

Hortiamide was originally isolated from the tropical plant genus Hortia and is a type of alkaloid compound unique to this genus. Hortia plants are widely distributed in tropical regions of South America, and their roots, stems, and leaves all contain this compound. Typical extraction processes include:

1. Sample collection and pretreatment: Fresh plant material is collected, air-dried or low-temperature dried, and crushed into fine powder.
2. Solvent extraction: Methanol or ethanol is used as the solvent for extraction extraction, commonly using ultrasound-assisted extraction or reflux extraction to improve extraction efficiency.
3. Crude extract separation: Fat-soluble impurities are removed by liquid-liquid separation method to obtain medium-polar extracts rich in hortiamide.
4. Column chromatography purification: Separation and purification are performed using silica gel column chromatography or reversed-phase high-performance liquid chromatography (RP-HPLC), combined with mass spectrometry and nuclear magnetic resonance (NMR) to confirm the structure.
5. Crystallization and drying: The purified hortiamide crystallizes to obtain a high-purity product.

In recent years, with advances in extraction technology, supercritical CO_2 extraction and membrane separation techniques have also been attempted for efficient hortiamide extraction, significantly improving yield and purity.

Pharmacological activity research

The pharmacological activity of hortiamide is mainly focused on antitumor effects, demonstrating multi-target regulatory capability. In vitro cell experiments showed that it had a significant proliferation inhibition effect on various tumor cell lines, with IC_50 values generally below 10 μM, demonstrating good cytotoxicity selectivity.

Antitumor activity

• Cell proliferation inhibition: Hortiamide can significantly inhibit the proliferation of breast, lung, colorectal, and multiple myeloma cells.
• Induced apoptosis: By regulating BCL2 family proteins, especially downregulating anti-apoptotic proteins MCL1 and BCL2, tumor cell apoptosis is promoted.
• Inhibition of tumor migration and invasion: Significantly reduces the expression of matrix metalloproteinase MMP2, inhibiting tumor cell migration and invasion capabilities.
• Anti-angiogenesis: By inhibiting HIF1A expression, it blocks the angiogenesis process induced by tumor hypoxia.
• Regulatory signaling pathways: Inhibits the STAT3 and MAPK1 signaling pathways, blocking tumor cell proliferation and survival signals.

Other potential activities

Preliminary studies also found that hortiamide may have anti-inflammatory and immunomodulatory effects, but the related mechanisms remain unclear and require further in-depth study.

Mechanism of action and molecular targets

The multi-target mechanism of hortiamide is a key foundation for its antitumor activity. Through molecular docking and cell signaling pathway analysis, hortiamide mainly targets the following key points:

• MCL1 and BCL2: These two anti-apoptotic proteins are key factors for tumor cell survival. Hortiamide promotes mitochondrial pathway-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 stromal processes. Hortiamide reduces the activity and expression of MMP2, inhibiting tumor metastasis.
• TOP1 and TOP2A: Topoisomerases are key enzymes for DNA replication and transcription. Hortiamide inhibits 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 regulates estrogen receptors (ESR1) and aromatases (CYP19A1), which may affect hormone levels and signaling.

The synergistic regulation of these targets enables Hortiamide to exert broad-spectrum anticancer effects across multiple tumor types.

Druggability evaluation and pharmacokinetics

Hortiamide's druggability evaluation shows it has good drug development potential:

• Molecular weight and Lipinski rule: molecular weight 309.4, complies with the Lipinski Five Rules, which is beneficial for oral absorption.
• Lipid solubility and polarity: LogP was 4.17, moderately high, indicating good lipid solubility and favorable cell membrane penetration, but attention should be paid to the impact of low water solubility on bioavailability.
• Water solubility: 0.0144 mg/mL, which is relatively low, suggesting that formulation optimization is needed to improve solubility.
• Blood-brain barrier permeability: High, indicating its potential for treating central nervous system-related tumors.
• Safety: No hERG channel suppression, Ames test negative, indicating lower risk of cardiotoxicity and genotoxicity.

Pharmacokinetic studies show that hortiamide is well absorbed orally and has a moderate plasma half-life. It is mainly metabolized by the liver, with bile as the primary excretion pathway. The metabolites are not yet fully understood, and further research is needed on their metabolic stability and potential drug interactions.

Prospects and outlooks for clinical applications

Based on hortiamide's multi-target antitumor mechanism and excellent druggability, its clinical application prospects are broad. Especially in treating drug-resistant tumors and multidrug combination therapies, hortiamide is expected to play an important role. Future research directions include:

• Drug formulation development: To address its low water solubility, new drug delivery systems such as nanocarriers and liposomes are developed to improve bioavailability.
• Combination therapy strategy: Combine with existing chemotherapy or targeted drugs to evaluate synergistic effects and reduce resistance risk.
• Preclinical safety evaluation: Systematic toxicological and pharmacokinetic studies lay the foundation for clinical trials.
• Clinical trial design: Early clinical trials focus on high-incidence tumors such as breast and lung cancer, evaluating efficacy and safety.
• In-depth mechanistic research: Using genomics and proteomics techniques to further elucidate its network of action and potential new targets.

In addition, hortiamide's potential in neurological tumors and inflammation-related diseases is also worth noting.

Conclusion

As a natural product with significant antitumor activity, hortiamide demonstrates broad drug development potential due to its unique chemical structure, multi-target mechanism, and excellent druggability. Although research on its pharmacological mechanisms and clinical applications is still in its early stages, existing data fully support its value as a candidate molecule for new anti-cancer drugs. In the future, through multidisciplinary collaboration, in-depth mechanistic research, pharmacokinetic optimization, and clinical translation, hortiamide is expected to advance its clinical application and benefit a wide range of cancer patients.