Fluoroquinolone-based Organic Salts and Ionic Liquids as Highly Bioavailable Broad-Spectrum Antimicrobials

The development of novel antibiotics did not present significant progress over the last years due to low returns, in particular regarding clinical trials. The majority of antibiotics display low permeability across biological membranes and/or reduced solubility in water, as well as polymorphic structures with different pharmaceutical activities. Ultimately, these disadvantages lead to low efficiency of the antibacterial drugs. Several strategies have been devised by Pharma in order to address these issues, namely prodrugs, solid dispersions, micelles, organic salts, among others.

The development of Organic Salts and Ionic Liquids (OSILs) from Active Pharmaceutical Ingredients (API-OSILs) has risen in the academia, and has recently reached Pharma, as an alternative to improve the properties of current drugs, in particular bioavailability, chemical and thermal stability, safety and therapeutic efficiency.

In our lab, we have successfully combined β-lactam, carbapenems, cephalosporins and fluoroquinolones as anions with biocompatible organic cations such as choline, alkylpyridiniums and alkylimidazoliums. Additional API-OSILs based on fluoroquinolones as cations were also synthesized by direct protonation with organic carboxylic and sulfonic acids. Overall, very interesting chemical and biological improvements have been observed.

In this communication we present our continuing work on fluoroquinolone-based OSILs, aiming at further improving the physicochemical and pharmaceutical properties of these promising salts. Water solubility, permeability and also in vitro cytotoxicity and antimicrobial activity of these compounds will be presented and discussed.