Title:Nitroimidazoles, Quinolones and Oxazolidinones as Fluorine Bearing Antitubercular Clinical Candidates
Volume: 15
Issue: 14
Author(s): Rahul V. Patel, Young-Soo Keum and Se Won Park
Affiliation:
Keywords:
Antitubercular drugs, delamanid, fluorine-containing drugs, gatifloxacin, linezolid, moxifloxacin, pretomanid, sutezolid.
Abstract: Tuberculosis is a leading killer of lives worldwide and the global curse of multi-drug
resistant tuberculosis is attaining really dangerous levels. Synergistic interaction of HIV and TB is the
twin epidemics in resource-limited countries as each potentiate progression of the other. The
increasing emergence of MDR-TB and XDR-TB place an immense burden for the treatment of TB
with currently available drugs. The situation urgently demands for the discovery of new drugs with
novel mode of action and differs in structural features in order to overcome resistance appears in conventional TB
therapeutics. The present report covers the discovery of three classes of antituberculosis drugs, Nitroimidazoles,
Quinolones and Oxazolidinones, undergoing clinical development with fluorine atom in their structures. Highly
electronegative fluorine atom plays a signature role in advancing medicinal innovations as it existence in the drug
compounds critically influences metabolic stability and lipophilicity thereby delaying its elimination by the body which
results into a long term in vivo efficiency of the drug. Presence of fluorine atom(s) in the drug structures described in this
report, has been associated with the several fold increase in the overall potency of the compound as demonstrated since
the early discoveries. 6 Fluorinated derivatives from these three classes as pretomanid, delamanid, moxifloxacin,
gatifloxacin, linezolid and sutezolid have been discussed with their antituberculosis effects, mode of action, chemical
synthetic routes and results of clinical studies.
