Marner, MichaelMichaelMarnerKulhanek, NiclasNiclasKulhanekEichberg, JohannaJohannaEichbergHardes, KorneliaKorneliaHardesMolin, Michael DalMichael DalMolinRybniker, JanJanRybnikerKirchner, MichaelMichaelKirchnerSchäberle, Till F.Till F.SchäberleGöttlich, RichardRichardGöttlich2025-11-182025-11-182024https://jlupub.ub.uni-giessen.de/handle/jlupub/21061https://doi.org/10.22029/jlupub-20410Tuberculosis has remained one of the world's deadliest infectious diseases. The complexity and numerous adverse effects of current treatment options as well as the emergence of multi-drug resistant M. tuberculosis (Mtb) demand research and innovation efforts to yield new anti-mycobacterial agents. In this study, we synthesized a series of imidazo[1,5-a]quinolines, including 4 new analogs, and evaluated their activity against Mtb. Inspired by previous studies, we also designed 8 compounds featuring a coordinated metal ion, determined their absolute configuration by single-crystal X-ray diffraction and included them in the bioactivity study. Remarkably, the metal complexation of 5c with either Zn2+ or Fe2+ increased the Mtb inhibitory activity of the compound 12.5-fold and reduced its cytotoxicity. Ultimately, out of the 21 analyzed imidazo[1,5-a]quinoline analogs, two zinc complexes (C1 and C7) showed the strongest, specific activity against Mtb H37Rv in vitro (IC90 = 7.7 and 17.7 μM).enNamensnennung 3.0 Internationalddc:540