Title:Old Drugs and New Targets as an Outlook for the Treatment of Tuberculosis
Volume: 25
Issue: 38
Author(s): Jan Zitko*Martin Doležal
Affiliation:
- Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy in Hradec Kralove, Charles University, Hradec Kralove,Czech Republic
Keywords:
Antitubercular, mechanism of action, tuberculosis, repurposed drugs, repositioned drugs, promiscuous
drugs, multitarget drugs.
Abstract: Background: Despite of the globally positive trends in the epidemiology of tuberculosis, the
increasing rates of drug-resistant strains are urging to introduce new antituberculars into clinical practice.
Development of a new chemical entity from hit to marketed drug is an extremely time and resources
consuming process with uncertain outcome. Repurposing of clinically used drugs can be a
cheaper alternative to develop new drugs effective in the treatment of tuberculosis.
Objective: To extract the latest information on new mechanisms of action described or proposed for
clinically used antitubercular drugs. To identify drugs from various pharmacodynamic groups as candidates
for repurposing to become effective in combatting tuberculosis. Attention will be paid to elucidate
the connection between repurposed drugs and new antituberculars in clinical practice or in clinical trials.
Methods: Scientific databases were searched for the keywords.
Results: We reviewed the latest aspects of usage and new mechanisms of action for both first-line and
second-line antitubercular drugs in clinical practice. Further, we found that surprisingly large number of
clinically used drugs from various pharmacodynamic groups have potential to be used in the treatment
of tuberculosis, including antimicrobial drugs not typically used against tuberculosis, statins, CNS
drugs (tricyclic phenothiazines, antidepressants, anticonvulsants), non-steroidal anti-inflammatory
drugs, kinase inhibitors, and others (metformin, disulfiram, verapamil, lansoprazole). Repurposed drugs
may become effective antituberculars, acting either by direct effects on mycobacteria or as adjunct,
host-directed therapy.
Conclusion: In this review, we showed that proper research of old drugs is a very efficient tool to develop
new antituberculars.
