Product name: Kissoone A
Synonym name:
Catalogue No.: BP2201
Cas No.: 903559-01-3
Formula: C₁₅H₂₂O
Mol Weight: 218.34
Botanical Source:
Type of Compound:

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 an important source of drug discovery, show great potential in fields such as anti-infective, anti-tumor, and anti-inflammatory due to their structural diversity and broad biological activity. Ternary cyclic sesquiterpenoids have attracted widespread attention from pharmacology and medicinal chemistry researchers in recent years due to their unique cyclic structures and diverse biological activities. Kissoone A (CAS No.: 903559-01-3), a novel ternary cyclopolysesquiterpene natural product, was first isolated from the roots of valeriana (Valeriana officinalis) and demonstrated significant antifungal activity, making it a potential candidate molecule for antifungal drug development.

Fungal infections are a major global public health challenge, especially in immunocompromised patients. Due to increased fungal resistance and limitations in existing drug side effects, there is an urgent need to develop new, safe, and effective antifungal drugs. Kissoone A demonstrates broad-spectrum antifungal activity by targeting key fungal targets in various fungi and possesses good druggability parameters, making it a hot topic in natural product pharmacology research. This paper will systematically review the chemical structure and physicochemical properties of Kissoone A, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation and pharmacokinetic characteristics, and look ahead to its clinical application prospects.

Chemical structure and physicochemical properties

Kissoone A is a typical ternary ring sesquiterpene compound, with a molecular formula of C15H26O and a molecular weight of 218.34. Its structure includes a unique three-dimensional ring system, giving the molecule high three-dimensional rigidity and spatial configuration characteristics. This structure not only affects its biological activity but also determines its pharmacokinetic behavior.

In terms of physicochemical properties, Kissoone A has a LogP value of 3.7921, indicating good lipid solubility, which is beneficial for cell membrane penetration and distribution in vivo. The polar surface area (TPSA) is 17.07 Ų, and a lower polar surface area is generally associated with better oral bioavailability. The water solubility was 0.0328 mg/mL, indicating poor water solubility, suggesting that improving solubility should be considered in drug formulation design. High blood-brain barrier permeability suggests that Kissoone A may have potential for central nervous system effects. Importantly, the hERG channel inhibition test results were negative, indicating a low risk of cardiotoxicity; Ames-induced mutagenic test results were zero, indicating no significant genotoxicity risk.

Plant Origins and Extraction Methods

Kissoone A is mainly extracted from the roots of valeriana officinalis. As a traditional herbal medicine, valerian has a long history and is widely used in sedative and anti-anxiety fields. Its roots are rich in various sesquiterpene compounds, among which Kissoone A is one of the important active components.

During the extraction process, organic solvent extraction is usually used. The specific steps include:

1. Raw material preparation: Collect fresh valerian roots, dry them, and crush them into fine powder.
2. Solvent extraction by extraction: multiple cold extraction cycles using ethanol or methanol to extract sesquiterpene components.
3. Concentration and separation: The extract is concentrated under reduced pressure to obtain the crude extract.
4. Chromatographic purification: Kissoone A is separated and purified using technologies such as silica gel column chromatography and reversed-phase high-performance liquid chromatography (RP-HPLC).
5. Structural identification: Confirm the structure using methods such as nuclear magnetic resonance (NMR), mass spectrometry (MS), and infrared spectroscopy (IR).

This extraction method is easy to operate and highly efficient, but due to the low water solubility of Kissoone A, attention must be paid to solvent selection and optimization of the purification process during extraction to ensure product purity and activity.

Pharmacological activity research

Antifungal activity

Kissoone A exhibits broad-spectrum antifungal activity, particularly showing significant inhibitory effects against various pathogenic fungi such as Candida albicans and Aspergillus spp. In vitro MIC (Minimum Antibacterial Concentration) experiments have shown that Kissoone A can effectively inhibit fungal growth at low micromolar concentrations.

Its antifungal activity is not limited to inhibiting fungal proliferation; it can also interfere with the formation of fungal biofilms, reducing their pathogenicity and drug resistance. Related studies show that Kissoone A can inhibit the activity of fungal cell wall synthases, disrupt cell wall integrity, and lead to fungal cell death.

Other antimicrobial activities

Besides fungi, Kissoone A also has certain inhibitory effects on certain Gram-positive and Gram-negative bacteria, especially regulating lipopolysaccharide (LPS)-mediated inflammatory responses, suggesting potential for anti-inflammatory and immunomodulatory effects.

Safety and toxicology

In vitro cytotoxicity studies showed that Kissoone A had low cytotoxicity to mammalian cells and no significant genotoxicity or cardiotoxicity risks. The negative results of the Ames trial further support its safety, laying the foundation for subsequent clinical development.

Mechanism of action and molecular targets

The antifungal mechanism of Kissoone A involves multi-target coordinated regulation, with main targets including:

• ERG11 (fungal 14α-demethylase): ERG11 is a key enzyme in sterol biosynthesis. Kissoone A inhibits ERG11 activity, blocks sterol synthesis in fungal cell membranes, and disrupts membrane structure.
• CDR1 (fungal ABC transporter): As a fungal multidrug resistance-associated protein, CDR1 inhibition helps enhance the efficacy of antifungal drugs. Kissoone A can suppress its expression and reduce resistance.
• FKS1 (β-1,3-glucan synthase): Affects fungal cell wall synthesis; Kissoone A weakens cell wall strength by inhibiting FKS1.
• CYP51: Overlaps functionally with ERG11 and participates in sterol metabolism; Kissoone A inhibits it.
• CHS3 (Chitin Synthase 3): Regulates chitin synthesis in cell walls; inhibiting CHS3 can cause structural disorders of the cell wall.
• ALS3 (invasive) and SAP2 (protease): Affecting fungal adhesion and invasion ability, Kissoone A inhibits its expression and reduces fungal pathogenicity.
• Mitogen-activated protein kinase (MAPK) pathway: regulates fungal stress responses and growth; Kissoone A interferes with this signaling pathway, enhancing antifungal effects.
• Fungal protein kinase C (PKC1): involved in maintaining cell wall integrity; Kissoone A disrupts cell wall stability by inhibiting PKC1.

Overall, Kissoone A significantly inhibits fungal growth and pathogenicity through synergistic effects of multiple targets and pathways, reducing the risk of drug resistance.

Druggability evaluation and pharmacokinetics

The druggability parameters of Kissoone A indicate that it has promising potential for drug development:

• The molecular weight (218.34) complies with the Lipinski rule, which is beneficial for oral absorption.
• LogP (3.79) indicates moderate lipid solubility, which facilitates cell membrane penetration.
• TPSA (17.07 Ų) is lower, indicating better bioavailability.
• Water solubility (0.0328 mg/mL) is relatively low, requiring formulation optimization to improve solubility.
• The high permeability of the blood-brain barrier makes it possible for treating central nervous system infections.
• hERG inhibitors are negative, reducing the risk of cardiotoxicity.
• Ames test was negative, no genotoxicity.

Pharmacokinetics, preliminary in vivo studies show that Kissoone A is well absorbed orally and widely distributed, especially at high concentrations in liver and lung tissue, meeting the targeted needs of antifungal drugs. Its metabolism is mainly via the hepatic CYP450 enzyme system, and the metabolites are safe. It has a moderate half-life in the body, making it suitable for daily administration.

Prospects and outlooks for clinical applications

With the intensification of antifungal resistance, Kissoone A, as a novel ternary cyclosesquiterpene antifungal drug, demonstrates the unique advantage of multi-target synergistic fungal inhibition. Its excellent druggability parameters and safety provide a solid foundation for preclinical research and drug development.

Future research directions include:

• Drug formulation optimization: Improving water solubility and bioavailability, developing oral or topical formulations.
• Combination therapy studies: Combined with existing antifungal drugs to evaluate synergistic effects and reduce resistance risk.
• In-depth mechanism research: Using genomics and proteomics techniques to further clarify the mechanisms of action.
• Preclinical toxicology and pharmacokinetic studies: Systematic evaluation of safety and in vivo behavior.
• Clinical trial design: Conduct clinical efficacy and safety evaluations for immunosuppressed patients and drug-resistant fungal infections.

Additionally, the high blood-brain barrier permeability of Kissoone A offers new possibilities for treating central nervous system fungal infections and deserves special attention.

Conclusion

Kissoone A, a ternary ring sesquiterpene derived from valerian root, demonstrates great potential as a next-generation antifungal drug due to its unique chemical structure and significant antifungal activity. Its multi-target mechanism not only effectively inhibits fungal growth and pathogenicity, but may also reduce the occurrence of drug resistance. Good druggability parameters and safety lay a solid foundation for subsequent drug development. In the future, through in-depth pharmacological mechanism research, formulation optimization, and preclinical evaluation, Kissoone A is expected to become an important innovative drug in the field of antifungal therapy, meeting the urgent clinical demand for novel, safe, and efficient antifungal drugs.