Synthesis, characterization and molecular docking study of novel bile acid curcumin conjugates as potent antibacterial and antibiofilm agents
摘要
Two novel bile acid–curcumin conjugates were synthesized via esterification of curcumin with cholic acid and deoxycholic acid. FT-IR, 1H &13C NMR and HPLC spectral data were employed to characterize the synthesized conjugates. Conjugate 3a exhibited significant antibacterial activity against Pseudomonas putida (ATCC 25922) with an IC₅₀ 4.48 ± 0.2 µg/mL. Conjugate 3b showed efficacy against Bacillus megaterium (QMB 1551) with an IC₅₀ of 7.02 ± 0.4 µg/mL. Both conjugates demonstrated higher antibacterial efficacy compared to curcumin, which had IC₅₀ values of 46.09 ± 2.6 and 76.02 ± 5.2 µg/mL, respectively. Conjugate 3a showed strong antibiofilm activity it reduced biofilm biomass of Bacillus megaterium (QMB1551) and Lactococcus lactis (NZ900) by nearly 90% at a concentration of 80 µg/mL. It also inhibited approximately 50% of biofilm formation in L. lactis and P. putida, with MIC₅₀ values of 24.8 ± 1.3 and 28.3 ± 0.4 µg/mL, respectively. In silico analysis showed Conjugate 3a exhibited a binding affinity of − 7.11 kcal/mol against bacterial outer membrane protein (PDB ID: 4RHB), compared to curcumin’s − 2.99 kcal/mol. Moreover, the conjugate 3a exhibited a higher affinity − 8.12 kcal/mol than curcumin − 6.49 kcal/mol against the cell division protein (PDB ID: 6LL6). These results highlight the enhanced ability of conjugate 3a to interact with and inhibited essential bacterial targets, supporting its potential as a promising antibacterial agent.