Multi-target antitubercular drugs: identification of novel dual MbtI and MptpB inhibitors

Tuberculosis, the infectious disease caused by Mycobacterium tuberculosis, has high levels of mortality worldwide and has already gained resistance to first- and second-line drugs. In this context, the study of new chemical entities with promising activities assumes paramount importance for the improvement of the current therapeutic strategies in the treatment of the patients affected with this disease. In particular, the development of multi-target agents has significantly grown in recent years, due to the reduction of financial costs and to the more pronounced therapeutic activity that they can exert, becoming one of the main research topics in the pharmaceutical industry. In this poster, we report the identification of a new class of compounds that can simultaneously interact with two molecular targets of Mycobacterium tuberculosis, namely MbtI and MptpB, already validated for the development of novel antitubercular agents. Among a series of competitive furan-based inhibitors of MbtI previously discovered by our research group,4 we disclosed promising ligands of MptpB, showing IC50 values in the range of about 30 μM. These preliminary results may be useful for the rational design of new derivatives, with the aim of increasing their inhibitory potency.