Synthesis and Biological Evaluation of Bile Acid–Triclosan Conjugates: A Study on Antibacterial, Antibiofilm, and Molecular Docking

This work describes the synthesis, characterization, and antibacterial properties of four bile acid-triclosan conjugates. The in vitro antibacterial activity of synthetic bile acid-triclosan conjugates was investigated against a panel of Gram-positive and Gram-negative bacteria. Conjugates <b>3</b> and <b>4</b> show high activity against <i>Escherichia coli</i> (ATCC25922), with IC₅₀ values of 2.94 ± 0.7 and 1.51 ± 0.05 μM, respectively. Conjugate <b>4</b> demonstrated 9 times the activity of triclosan (6.77 μM) and 18 times the potency of kanamycin, a well-known antibiotic. Compound <b>3</b> showed higher potential activity against all evaluated strains, including <i>Bacillus megaterium</i> (IC₅₀: 3.05 ± 0.02), <i>Bacillus amyloquefaciens</i> (IC₅₀: 8.79 ± 0.01), <i>Serratia marcescens</i> (IC₅₀: 6.77 ± 0.4), and <i>E. coli</i> (IC₅₀: 1.51 ± 0.05 μM). These findings indicate that it has broad-spectrum antibacterial activity. Bile acid-triclosan conjugates prevent biofilms by up to 99% at low doses (conjugates <b>4</b>; 4.16 ± 0.8 μM), compared to triclosan. Conjugate <b>5</b> was most potent against <i>B. amyloquefaciens</i> (IC₅₀ = 5.23 ± 0.2 μM), while conjugate <b>4</b> was most effective against <i>B. megaterium</i> (IC₅₀ = 4.16 ± 0.8 μM) in biofilm formation. These conjugates inhibit biofilm formation by limiting the extracellular polymeric substance generation. The in vitro antibacterial study revealed that bile acid-triclosan conjugates were more effective than the parent molecule triclosan at inhibiting bacterial growth and biofilm formation against both Gram-positive and Gram-negative bacteria.