Amide-functionalized cholic acid hybrids: design, bioactivity, and computational analysis.

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Computational Chemistry

Background:

• Cholic acid derivatives are explored for potential therapeutic applications.
• Developing multifunctional agents with both antioxidant and antibacterial properties is a key challenge in drug discovery.

Purpose of the Study:

• To synthesize and characterize novel amide-linked cholic acid derivatives.
• To evaluate the antioxidant and antibacterial potential of these synthesized compounds.
• To investigate the molecular interactions underlying their bioactivity using computational methods.

Main Methods:

• One-pot acyl chloride coupling strategy for synthesis.
• DPPH radical scavenging assay for antioxidant evaluation.
• Antibacterial assays against *Staphylococcus aureus* and *Escherichia coli*.
• In silico studies including molecular docking, molecular dynamics, and MM-PBSA.

Main Results:

• Structurally diverse cholic acid derivatives were successfully synthesized under mild conditions.
• Compounds 3b-d demonstrated significant antioxidant activity (average 50% DPPH scavenging).
• Compounds showed preferential antibacterial activity against Gram-positive bacteria, especially aromatic amide analogs.
• In silico analyses revealed stable binding modes and favorable energetics against bacterial DNA gyrase (GyrB).

Conclusions:

• The cholic acid scaffold can be modified to create multifunctional agents.
• The synthesized derivatives possess promising antioxidant and selective antibacterial properties.
• These findings provide a solid foundation for developing new antimicrobial drug candidates.