Hybridization approach to drug discovery inhibiting Mycobacterium tuberculosis. An overview

Tuberculosis is one of the top 10 causes of death worldwide and the leading cause of death from a single infectious agent mainly due to Mycobacterium tuberculosis (MTB). Recently, clinical prognoses have worsened due to the emergence of multi-drug resistant (MDR) and extensive-drug resistant (XDR) tuberculosis which lead to the need of new, efficient and safely drugs. Among the several strategies, polypharmacology could be considered one of the best solutions, in particular the multi-target directed ligands strategy (MTDLs), based on the synthesis of hybrid ligands acting against two targets of the pathogen. The framework strategy comprises linking, fusing and merging approaches to develop new chemical entities. With these premises, this review aims to provide an overview of recent hybridization approach, in medicinal chemistry, of the most recent and promising multitargeting antimycobacterial candidates.