Journal article

Authors list: Marner, Michael; Kulhanek, Niclas; Eichberg, Johanna; Hardes, Kornelia; Molin, Michael Dal; Rybniker, Jan; Kirchner, Michael; Schäberle, Till F.; Göttlich, Richard

Publication year: 2024

Pages: 1746-1750

Journal: RSC Medicinal Chemistry

Volume number: 15

Issue number: 5

eISSN: 2632-8682

Open access status: Hybrid

DOI Link: https://doi.org/10.1039/d4md00086b

Publisher: Royal Society of Chemistry

Abstract: 
Tuberculosis 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 mu M).

Harvard Citation style: Marner, M., Kulhanek, N., Eichberg, J., Hardes, K., Molin, M., Rybniker, J., et al. (2024) Design, synthesis and antimycobacterial activity of imidazo[1,5-a]quinolines and their zinc-complexes, RSC Medicinal Chemistry, 15(5), pp. 1746-1750. https://doi.org/10.1039/d4md00086b

APA Citation style: Marner, M., Kulhanek, N., Eichberg, J., Hardes, K., Molin, M., Rybniker, J., Kirchner, M., Schäberle, T., & Göttlich, R. (2024). Design, synthesis and antimycobacterial activity of imidazo[1,5-a]quinolines and their zinc-complexes. RSC Medicinal Chemistry. 15(5), 1746-1750. https://doi.org/10.1039/d4md00086b