Advancing infection therapy: the role of novel menthol-based antimicrobials

In this work, 17 derivatives were synthesised by combining halogenated and non-halogenated cinnamoyl scaffolds with menthol and tested against a panel of Gram-positive and Gram-negative bacteria. Among the synthesised derivatives, MF1 and MCl2 demonstrated enhanced therapeutic potential. MF1 showed the most potent antimicrobial activity (MIC values ranging from 8 to 64 mg/L against E. faecium), representing a significant improvement over menthol, with a five-fold reduction in MIC50. Additionally, MF1 effectively reduced biofilm biomass production by 50% in S. aureus and by 20% in P. aeruginosa at sub-MIC concentrations. MCl2 reduced biomass by up to 40% in A. baumannii at the lowest subMIC concentrations tested (0.06 x MIC). Moreover, MCl2 showed potential as a wound healing agent promoting fibroblast-mediated repair within just 24 h. Notably, both compounds exhibited no cytotoxic effects. Molecular docking and molecular dynamics simulations confirmed strong binding affinity and high stability of MF1 and MCl2 with the target protein.