Fluoroquinolone Derivatives in the Treatment of

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 poses an emergent public health threat. Fluoroquinolones are commonly used in the treatment of both MDR TB and drug-sensitive tuberculosis patients who are intolerant to first-line antitubercular agents. Unfortunately, these drugs have mild side effects, relevant to 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). Here, we developed esters as prodrugs of the fluoroquinolones levofloxacin and ciprofloxacin, with long-chain fatty alcohols. Both the alcohols and the quinolone have previously shown antimycobacterial activity and the aim was to develop esters with improved lipophilicity and capable of delivering the free acid inside mycobacterial cells. The carboxylic acid group of fluoroquinolones is essential to the mode of action but is also responsible for many of its side effects and metal-chelating properties. The synthesis, stability in biological media, and antibacterial activity were evaluated, the latter not only against