Exploring Benzo[h]chromene Derivatives as Agents against Protozoal and Mycobacterial Infections

In this study, the efficacy of benzo[h]chromene derivatives as antiprotozoal and antimycobacterial agents was explored. A total of twenty compounds, including benzo[h]chromene alkyl diesters and benzo[h]chromene-triazole derivatives, were synthesized and tested against , , , and strains of and LIID-01. Notably, compounds , , , and exhibited superior activity against , with IC values of 19.2, 37.3, 68.7, and 24.7 µM, respectively, outperforming the reference drug benznidazole (IC : 54.7 µM). Compounds and showed excellent selectivity indices against , with SI values of 19 and 18, respectively, suggesting they could be potential alternatives to the commonly used, but more selective, miltefosine (IC : 64.0 µM, SI: 43.0). Additionally, compounds , , and were most effective against , with IC values of 24.9, 30.5, and 46.6 µM, respectively. Compounds and were particularly potent against various strains, highlighting their significance given the inherent resistance of these bacteria to standard antimicrobials. The sensitivity of LIID-01 to these compounds also underscored their potential in managing infections by the Mycobacterium avium-intracellulare complex.