Tuberculosis drug development; fluoroquinolone structural tailoring

Tuberculosis (TB) is a contagious infectious disease caused by the bacillus Mycobacterium tuberculosis (Mtb). It is transmitted through small particles in the air (<5 µm) expelled by active tuberculosis patients; when inhaled by a new host, they can potentially cause infection. Nowadays, TB is still the major cause of morbidity and mortality by a single infectious agent, this is further exacerbated by the worldwide emergence of multidrug-resistant strains of Mtb. Thus, effective methods of diagnosis, prophylaxis, and new pharmacological therapies must be carried out in order to control this disease. Fluoroquinolones (FQ) are synthetic antibiotics with a broad spectrum against Gram-negative and Gram-positive bacteria, including M. tuberculosis. The treatment with FQ plays an important role in managing drug-resistant tuberculosis. Modifications on FQ structure have been extensively studied, thereby, four generations of FQ have emerged having a broad spectrum of antibacterial properties. These modifications improve the overall efficiency of FQ by increasing tissue penetration, reducing side effects, and addressing emerging bacterial resistance. In this scenario, current trends on FQ research have focused on new synthetic approaches that allow fluoroquinolones to address the worldwide issue of multidrug-resistant tuberculosis. The aim of this review is to highlight the overall effects of newly synthesized FQ molecules having antitubercular activity.