Tuberculosis (TB) is currently one of the leading causes of death due to infective agents and the growing rate of multidrug-resistant tuberculosis (MDR TB) cases, is an emergent public health threat. Fluoroquinolones are commonly used in the treatment of tuberculosis for drug-sensitive patients who are intolerant to first-line antitubercular agents, as well as in the case of MDR TB. Unfortunately, these drugs have mild side effects, relevant in the prolonged treatment regimens and diminished bioavailability due to binding of metal ions. Moreover the resistance to fluoroquinolones is also on the rise, a characteristic of extensively drug resistant TB (XDR TB).

With these issues in mind, the present work focus on masking the acid moiety of fluoroquinolones, essential to the mode of action but also responsible for many of its side effects and metal chelating properties. A secondary objective was the modulation of the lipophilicity of the compounds. This was achieved by preparing esters as a prodrug of the fluoroquinolones levofloxacin and ciprofloxacin, with medium to long chain fatty alcohols.

The synthesis, stability in biological media and antibacterial activity were evaluated, the latter not only against mycobacterium tuberculosis but also against other clinically relevant bacterial species, since the parent compounds display a broad spectrum of activity. The biological results show a reduction in the antitubercular activity of the synthesized derivatives, probably due to deficient activation of the ester prodrug, nonetheless it was observed that the derivatives retain bioactivity against other fluoroquinolone-resistant bacteria, indicating a different mode of action.