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.