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

Abstract

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 3 and 4 show high activity against Escherichia coli (ATCC25922), with IC₅₀ values of 2.94 ± 0.7 and 1.51 ± 0.05 μM, respectively. Conjugate 4 demonstrated 9 times the activity of triclosan (6.77 μM) and 18 times the potency of kanamycin, a well-known antibiotic. Compound 3 showed higher potential activity against all evaluated strains, including Bacillus megaterium (IC₅₀: 3.05 ± 0.02), Bacillus amyloquefaciens (IC₅₀: 8.79 ± 0.01), Serratia marcescens (IC₅₀: 6.77 ± 0.4), and E. coli (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 4; 4.16 ± 0.8 μM), compared to triclosan. Conjugate 5 was most potent against B. amyloquefaciens (IC₅₀ = 5.23 ± 0.2 μM), while conjugate 4 was most effective against B. megaterium (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.