Synonym name: 7-Methylaxillarin; Chrysosplenol D; Quercetagetin 3,6,7-trimethyl ether
Catalogue No.: BP0057
Cas No.: 14965-20-9
Formula: C₁₈H₁₆O₈
Mol Weight: 360.318
Botanical Source:

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams.

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

HPLC of 3,6,7-Trimethylquercetagetin

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

Introduction/Overview

3,6,7-Trimethylquercetagetin (CAS No.: 14965-20-9) is a naturally occurring trimethyloxyflavonoid with significant biological activity. As a derivative of quercetin, its structural modification gives it unique pharmacological properties. In recent years, with the deepening development of natural product pharmacology, 3,6,7-trimethyl querceran marigold has gradually become a research hotspot due to its multi-target and multi-mechanism mode of action, especially its potential application value in anti-tumor and endometriosis diseases.

This review aims to systematically summarize the chemical structure and physicochemical properties, plant origins and extraction methods, pharmacological activity, and mechanism of action of 3,6,7-Trimethyl querquer marigold, combined with its druggability parameters, to explore its prospects and challenges in clinical application, and to provide theoretical basis and research directions for subsequent drug development and clinical translation.

Chemical structure and physicochemical properties

3,6,7-Trimethyl querceranin marigold belongs to the flavonoid class, specifically trimethoxyflavone. Its chemical structure is based on the quercetin skeleton, with methyl ethers formed by methyl ether by methylation at positions 3, 6, and 7, significantly affecting its physicochemical properties and biological activity. The molecular formula is C18H16O8, molecular weight is 360.32, and the LogP value is about 2.5, indicating moderate lipid solubility, which facilitates cell membrane penetration.

The compound has a polar surface area (TPSA) of 131.39 Ų and a hydrogen bond acceptor count of 8, indicating strong hydrogen bond formation ability when binding to protein targets. Its low blood-brain barrier permeability suggests limited distribution in the central nervous system. Toxicological indicators showed no hepatotoxicity, cardiotoxicity, or hERG channel inhibition. Ames-induced mutagenic tests were negative, indicating high safety and good drug potential.

Plant Origins and Extraction Methods

3,6,7-Trimethyl oak marigoldin is mainly found in the genus Tagetes spp., a plant in the Asteraceae family, especially in the flowers and leaves of certain wild and cultivated varieties. These plants are widely distributed in the Americas and parts of Asia, and have a long history as both traditional herbal and ornamental plants.

The extraction process typically uses organic solvent extraction combined with column chromatography separation technology. Common solvents include methanol, ethanol, and ethyl acetate, which utilize their polarity differences to achieve effective separation. Modern extraction methods such as ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE) have been applied to improve extraction efficiency and purity. During purification, reversed-phase high-performance liquid chromatography (RP-HPLC) and preparative thin-layer chromatography (Prep-TLC) are common separation methods.

Additionally, identification methods mainly rely on mass spectrometry (MS), nuclear magnetic resonance (NMR), and UV-Vis spectroscopy (UV-Vis) analysis to ensure the structural accuracy and purity of compounds.

Pharmacological activity research

3,6,7-Trimethyl querceran marigold exhibits various pharmacological activities, with its antitumor and anti-endometriosis effects being particularly significant.

Antitumor activity

In vitro cell experiments have shown that this compound can inhibit the proliferation of various tumor cell lines, including breast cancer, lung cancer, and cervical cancer cells. Its mechanism of action involves inducing cell cycle arrest, promoting apoptosis, and inhibiting tumor cell migration and invasion. Related studies indicate that 3,6,7-trimethyl querceran marigold exerts antitumor effects by modulating multiple signaling pathways, such as PI3K/Akt, MAPK, and NF-κB.

Anti-endometriosis effect

Endometriosis is a gynecological disease characterized by the ectopic growth of endometrial tissue, with a complex pathological mechanism. 3,6,7-Trimethyl querceran marigold participates in inflammatory responses, hormone signaling regulation, and apoptosis by regulating various molecular targets such as MAOA, ESR1/2, ABCB1, APEX1, ABCG2, ALOX5, XDH, ADORA3, and TERT, thereby inhibiting abnormal proliferation and inflammation in diseased tissues.

Additionally, this compound has antioxidant and anti-inflammatory properties that help alleviate endometriosis-related symptoms and improve patients' quality of life.

Other pharmacological effects

Some studies have also found that 3,6,7-trimethyl querceran marigoldin has certain neuroprotective and immunomodulatory functions, but the related mechanisms still require further exploration.

Mechanism of action and molecular targets

The multi-target mechanism of 3,6,7-trimethyl querquer marigoldin forms the basis for its complex pharmacological effects. Its main targets and mechanisms of action include:

• MAOA (Monoamine Oxidase A): Regulates neurotransmitter metabolism, affects inflammation and cellular metabolic states, and participates in the pathological process of endometriosis.
• ESR1/ESR2 (estrogen receptors α/β): Regulates hormone signaling pathways, affects cell proliferation and apoptosis, and is key in endometriosis and hormone-dependent tumors.
• ABCB1/ABCG2 (ATP binding box transporter): involved in drug efflux and multidrug resistance, affecting tumor cell sensitivity to chemotherapy drugs.
• APEX1 (DNA repair enzyme): Participates in oxidative damage repair and maintains genome stability.
• ALOX5 (lipoxygenase 5): participates in the production of inflammatory mediators and regulates inflammatory responses.
• XDH (xanthine dehydrogenase): affects redox states and participates in cellular metabolism.
• ADORA3 (adenosine A3 receptor): regulates immune responses and apoptosis.
• TERT (telomerase reverse transcriptase): an important marker regulating cell proliferation and aging, and tumor cell activity.

By regulating these targets, 3,6,7-Trimethyl querquer marigoldin can intervene in cell signaling, metabolism, and gene expression, exerting multiple effects including anti-inflammatory, antioxidant, anti-proliferative effects, and pro-apoptosis.

Druggability evaluation and pharmacokinetics

Combined with druggability parameters, 3,6,7-Trimethyl querquer marigoldine exhibits good pharmacokinetics and safety profiles.

• Molecular weight and lipid solubility: A molecular weight of 360.32 and a LogP value of 2.5 comply with the Lipinski rule, indicating good oral bioavailability.
• Polar surface area (TPSA): 131.39 Ų, though slightly higher, still within an acceptable range, supporting effective binding to the target.
• Number of hydrogen bond receptors: 8 hydrogen bond receptors facilitate intermolecular interactions and enhance target affinity.
• Blood-brain barrier permeability: Low permeability reduces the risk of central nervous system side effects.
• Toxicological indicators: no hepatotoxicity, cardiotoxicity, or hERG suppression; Ames test was negative, indicating good safety.

Pharmacokinetic research is still in its early stages. In vivo, metabolic pathways may involve the liver CYP450 enzyme system, but specific metabolites and kinetic parameters require further systematic study.

Prospects and outlooks for clinical applications

Based on its multi-target and multi-mechanism pharmacological activity, 3,6,7-trimethylquerquer marigoldin shows broad application prospects in anti-tumor and endometriosis treatment. Its excellent safety and druggability provide a solid foundation for clinical translation.

Future research should focus on:

1. In-depth pharmacokinetics and toxicology evaluation to clarify in vivo metabolic pathways and long-term safety.
2. Optimizing formulations and delivery routes to improve bioavailability and targeting.
3. Design a multi-center preclinical and clinical trial to verify efficacy and safety.
4. Exploring combination drug strategies to work synergistically with existing drugs to improve treatment outcomes.
5. In-depth analysis of molecular mechanisms, using modern omics techniques to reveal their comprehensive network of actions.

Additionally, based on their structural characteristics, chemical modifications and derivative design are also important directions for future drug development.

Conclusion

3,6,7-Trimethyl querquer marigold, as a natural trimethoxyflavonoid product with significant biological activity, shows great potential in the treatment of anti-tumor and endometriosis due to its unique chemical structure and multi-target pharmacological effects. Its excellent druggability and safety lay the foundation for subsequent clinical applications.

In the future, through systematic pharmacokinetic studies, mechanistic analysis, and clinical validation, 3,6,7-Trimethyl querquer marigoldine is expected to become a model for natural product drug development, promoting the application and advancement of natural flavonoid compounds in modern medicine.