Chapter 28. Multi-target Compounds for Tuberculosis

Tuberculosis still remains an urgent global health problem, especially because of the spread of Mycobacterium tuberculosis strains resistant to currently available antitubercular drugs. In this context, polypharmacology, an approach involving the development of single molecules acting on different targets, could represent a strategy to overcome the problem of resistance emergence. Indeed, compared with the polypharmacy approach currently used in the treatment of tuberculosis, polypharmacology could have several advantages. First, the probability of developing resistance to a compound with multiple targets should be greatly reduced. In addition, these types of compounds should exert higher efficacy and possibly synergistic effects. Finally, a single molecule should plausibly be associated with a lower risk of side effects and drug–drug interaction. This chapter presents an overview of the most recent in silico , in vitro , and in vivo research aimed at identifying novel multitarget compounds, along with the most promising molecules that have emerged from these studies.