One-Step Organic Synthesis of 18ß-Glycyrrhetinic Acid-Anthraquinone Ester Products: Exploration of Antibacterial Activity and Structure-Activity Relationship, Toxicity Evaluation in Zebrafish.
Chem Biol Drug Des
; 104(3): e14631, 2024 Sep.
Article
in En
| MEDLINE
| ID: mdl-39317695
ABSTRACT
To combine the activity characteristics of 18ß-glycyrrhetinic acid (18ß-GA) and anthraquinone compounds (rhein and emodin), reduce toxicity, and explore the structure-activity relationship (SAR) of anthraquinones, 18ß-GA-anthraquinone ester compounds were synthesized by one-step organic synthesis. The products were separated and purified by HPLC and characterized by NMR and EI-MS. It was finally determined as di-18ß-GA-3-rhein ester (1, New), GA dimer (2, known), 18ß-GA-3-emodin ester (3, known), and di-18ß-GA-1-emodin ester (4, new). The MIC of three reactants and four products against Escherichia coli and Staphylococcus aureus were detected in vitro. Its developmental toxicity and cardiotoxicity were assessed using zebrafish embryos. The experimental results showed that rhein had the best antibacterial activity against Staphylococcus aureus with MIC50 of 2.4 mM, and it was speculated that -COOH, -OH, and intramolecular hydrogen bonds in anthraquinone compounds would enhance the antibacterial effect, while the presence of-CH3 might weaken the antibacterial activity. Product 1 increased the hatching rate and survival rate of zebrafish embryos and reduced the malformation rate and cardiomyocyte apoptosis. This experiment lays the foundation for further studying the SAR of anthraquinones and providing new drug candidates.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Staphylococcus aureus
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Zebrafish
/
Microbial Sensitivity Tests
/
Anthraquinones
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Escherichia coli
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Glycyrrhetinic Acid
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Anti-Bacterial Agents
Limits:
Animals
Language:
En
Journal:
Chem Biol Drug Des
Journal subject:
BIOQUIMICA
/
FARMACIA
/
FARMACOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: