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

Introduction/Overview

Mucic acid, also known as galactodiaic acid, is a hexacarboxylic acid compound formed by the cleavage of galactose through the formal oxidation ring cleavage. It has the molecular formula C6H10O8 and the CAS number is 526-99-8. As an important natural product and human metabolite, mucic acid plays a key role in the metabolic network of living organisms. In recent years, with the deepening development of natural product pharmacology, mucic acid, due to its unique chemical structure and multiple biological activities, especially its potential applications in the antibacterial field, has gradually attracted widespread attention from the scientific research community.

This review aims to systematically summarize the chemical structure and physicochemical properties of mucinic acid, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and pharmacokinetic characteristics, and to look ahead to its clinical application prospects. By integrating the latest research progress, it aims to provide theoretical basis and practical guidance for subsequent development of natural product drugs.

Chemical structure and physicochemical properties

Mucic acid is a complete oxidation product of galactose, structurally belonging to the hexacarboxylic acid compound, with a molecular weight of 210.1380. Its molecular structure contains six carbon atoms, each connected to a carboxyl group (–COOH), giving it high polarity and acidity. The chemical formula of mucic acid is C6H10O8, and its structural formula can be regarded as a linear hexacarboxylic acid formed by oxidative cleavage of galactose's cyclic structure.

In terms of physicochemical properties, mucic acid exhibits high water solubility (about 179 mg/mL), with a LogP value of -1.8370, indicating strong hydrophilicity and low lipid solubility. This property gives it good dispersibility in aqueous environments but limits its ability to penetrate lipid membranes. Mucic acid is polar in its relatively high topological pole surface area (TPSA) of 155.52 Ų, which usually means it has a lower ability to cross the blood-brain barrier, consistent with its pharmacokinetic characteristic of low blood-brain barrier permeability. Additionally, mucic acid showed no inhibitory activity on hERG channels, and Ames' mutagenicity test result was zero, indicating high safety and potential for drug development.

Plant Origins and Extraction Methods

Mucic acid, as an oxidation product of galactose, is widely present in various plant and microbial metabolites. Its natural sources mainly include plant polysaccharide degradation products rich in galactose, such as certain legumes, seaweed, and pectin compounds found in fruits. Galactopolysaccharides in plant cell walls can be produced by oxidase to produce mucic acid. Additionally, mucic acid can be detected during fermentation by certain fungi and bacteria.

Traditional extraction methods mostly rely on acidic hydrolysis and oxidation treatment of plant raw materials. The specific steps usually include:

1. Raw material pretreatment: Select plant tissue rich in galactose, dry and crush it.
2. Acid hydrolysis: uses dilute acids (such as sulfuric acid) to hydrolyze plant polysaccharides, releasing galactose.
3. Oxidative ring lysis: Galactose is oxidized to mucilic acid by chemical oxidants (such as nitric acid).
4. Purification and separation: Using crystallization, recrystallization, or ion exchange resins to separate and purify viscoic acid.

In recent years, advances in green chemistry and biocatalysis technologies have driven innovation in mucic acid extraction methods. For example, using microbial fermentation to directly convert galactose into mucic acid, or using enzyme-catalyzed oxidation instead of traditional chemical oxidation, significantly increases yield and purity, and reduces environmental pollution.

Pharmacological activity research

Pharmacological studies on mucic acid mainly focus on its antibacterial effects. Multiple in vitro experiments have shown that mucic acid inhibits various Gram-positive and Gram-negative bacteria. Its antibacterial spectrum covers common pathogens such as Staphylococcus aureus, Escherichia coli, and Streptococcus pneumoniae, demonstrating broad antibacterial potential.

In addition, mucic acid also shows certain activity in the antifungal field, especially in its significant inhibition of yeast and certain skin fungi. Its antibacterial activity is related to its polycarboxylic acid structure and may be achieved by interfering with bacterial cell wall synthesis, membrane function, and metabolic pathways.

In addition to its antibacterial effects, mucic acid has been reported to have potential antioxidant, anti-inflammatory, and metabolic effects related to cell metabolism. Although related research is still in its early stages, these multiple biological activities provide rich directions for pharmacological studies of mucic acid.

Mechanism of action and molecular targets

The antibacterial mechanism of mucic acid is not yet fully elucidated, but based on existing target analysis and molecular docking studies, its mechanism of action is speculated to involve multi-target synergistic interaction. The main targets include:

• DNA gyrase A (GYRA): As a key enzyme for bacterial DNA replication, mucic acid may inhibit GYRA activity and block bacterial DNA replication, achieving antibacterial effects.
• Cell membrane proteins (GYPB, MECA): Mucinous acid may interfere with the integrity and function of bacterial cell membranes, leading to changes in membrane permeability.
• Cell division protein (FTSZ): Affects bacterial cell division and inhibits bacterial proliferation.
• Fatty Acid Synthase (FABI): Disrupts lipid synthesis in bacterial cell membranes by inhibiting fatty acid biosynthesis.
• Dihydrofolate reductase (DHFR): blocks bacterial folate metabolism and inhibits nucleic acid synthesis.
• Fungus-specific targets (ERG11, CYP51A1): Inhibit the synthesis of ergosterol in fungal cell membranes, disrupting the stability of the fungal membrane.
• Multidrug resistance protein (CDR1): May enhance the effectiveness of antifungal drugs by inhibiting fungal drug efflux pumps.

The multiple mechanisms of action of these targets give mucic acid broad application prospects in antimicrobial therapy, especially in the prevention and control of drug-resistant strains.

Druggability evaluation and pharmacokinetics

Druggability evaluation is a crucial step in the development of natural product drugs. The physicochemical properties of mucic acid show good water solubility and low lipid solubility, making it suitable for oral or topical administration. Its LogP value was -1.8370, indicating that its in vivo distribution tends toward aqueous environments and makes it difficult to penetrate lipid membrane structures such as the blood-brain barrier, consistent with experimental data indicating low permeability of the blood-brain barrier.

In terms of safety, mucic acid did not show hERG channel inhibition, reducing the risk of cardiotoxicity; The Ames test result was negative, indicating no significant mutagenicity. Additionally, mucic acid, as a metabolite in the human body, has good biocompatibility and metabolic stability.

Pharmacokinetic studies show that mucic acid is mainly excreted in the body through the kidneys, with bioavailability limited by its polarity and molecular size. It is absorbed quickly, but its distribution is limited, and its metabolic pathway requires further study. In the future, structural modification or vector system optimization may improve its pharmacokinetic properties.

Prospects and outlooks for clinical applications

The antibacterial activity and good safety profile of mucic acid provide a solid foundation for its clinical application. As antibiotic resistance becomes increasingly severe, developing new antimicrobials has become a global focus of medical research. Mucic acid, as a natural product with multi-target action, is expected to become a candidate molecule for new antibacterial drugs.

Future research should focus on:

• Structural optimization and derivative development: Chemical modification enhances the membrane permeability and targeting of mucinic acid, enhancing its antibacterial efficacy.
• Drug carrier systems: Utilize nanocarriers, liposomes, and other technologies to improve the in vivo stability and targeted delivery of mucinic acid.
• Combination therapy strategy: Used in combination with existing antibiotics to overcome resistance and achieve synergistic effects.
• Preclinical and clinical research: Systematic evaluation of pharmacodynamics, toxicology, and pharmacokinetics, promoting clinical translation.

Moreover, the potential of mucic acid in other pharmacological fields such as anti-inflammatory and antioxidant properties is worth further exploration, providing possibilities for multifunctional drug development.

Conclusion

Mucic acid, as a widely sourced and structurally unique natural product, has become a hot topic in pharmacological research due to its remarkable antibacterial activity and good safety. Through a systematic review of its chemical properties, pharmacological mechanisms, and druggability characteristics, this paper provides theoretical support and research directions for the drug development of mucinic acid. In the future, with technological advances and deeper research, mucic acid is expected to play an important role in the field of antimicrobial drugs, becoming a powerful weapon in addressing the challenges of antibiotic resistance.