Abstract

Introduction: An attractive antibiotic-adjuvant strategy consisting of the design and synthesis of polyaminoisoprenyl molecules able to restore the antibiotic activity of tetracycline antibiotics against resistant Pseudomonas aeruginosa bacterial strains has been developed.

Methods: These chemo-sensitizers are readily prepared from geraniol and farnesol in an efficient two steps synthesis with good to moderate yields varying from 38 to 64% and leading to a significant decrease in antibiotic resistance.

Results: Thus, the influence of the nature of the tetracycline antibiotic used as well as the structure of the polyaminoisoprenyl derivatives involved in the outcome of the antibiotic-adjuvant combination against P. aeruginosa resistance to tetracyclines were investigated.

Conclusion: Additionally, our data suggested that their mechanism of action is closely associated with the increase of the outer-membrane permeability.

Keywords: Polyaminoisoprenyl derivatives, antibiotic adjuvants, polyamines, Pseudomonas aeruginosa, tetracycline antibiotic.

Graphical Abstract