Lithocholic acid and derivatives: Antibacterial activity

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Microbiology

Background:

• Lithocholic acid (LCA) is a secondary bile acid with known biological activities.
• Developing novel bioactive compounds from natural scaffolds is crucial for drug discovery.
• Modifying bile acids can lead to derivatives with enhanced or altered pharmacological properties.

Purpose of the Study:

• To synthesize novel semi-synthetic lithocholic acid derivatives.
• To evaluate the antibacterial activity of these derivatives against Gram-positive and Gram-negative bacteria.
• To investigate the potential of active derivatives to modify bacterial susceptibility to antibiotics.

Main Methods:

• Fifteen semi-synthetic lithocholic acid derivatives were prepared via modifications at C-3 and/or C-24.
• Compound structures were confirmed using spectroscopic techniques (IR, MS, 1D- and 2D-NMR).
• Minimum Inhibitory Concentrations (MICs) were determined for bacterial growth inhibition (Escherichia coli, Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa).
• Susceptibility testing of bacterial pathogens to aminoglycoside antibiotics was performed for active derivatives.

Main Results:

• Synthesis yielded compounds with 37% to 100% reaction efficiency.
• The derivative 3α-formyloxy-5β-cholan-24-oic acid (LA-06) exhibited potent activity.
• LA-06 showed MIC values of 0.0790 mM against E. coli and B. cereus, and 0.0395 mM against S. aureus.
• Several lithocholic acid derivatives displayed MIC values less than or equal to 1.2 mM.

Conclusions:

• Novel lithocholic acid derivatives were successfully synthesized and characterized.
• LA-06 demonstrates significant broad-spectrum antibacterial activity.
• These findings suggest potential for lithocholic acid derivatives as standalone antimicrobials or as agents that modulate antibiotic efficacy.