Antimicrobial evaluation of neutral and cationic iridium(III) and rhodium(III) aminoquinoline-benzimidazole hybrid complexes

• DOI: 10.1016/j.ejmech.2020.112694
• Publication Date: 2020-08-05T01:41:09Z
• Authors: Nadia Baartzes; Audrey Jordaan; Digby F. Warner; Jill Combrinck; Dale Taylor; Kelly Chibale; Gregory S. Smith
• Keywords: Plasmodium falciparum; CHO Cells; Mycobacterium tuberculosis; Iridium; 01 natural sciences; Drug Resistance, Multiple; 0104 chemical sciences; 3. Good health; Cricetulus; Anti-Infective Agents; Coordination Complexes; Aminoquinolines; Animals; Benzimidazoles; Rhodium

A series of neutral and cationic Ir(III) and Rh(III) aminoquinoline-benzimidazole hybrid complexes were synthesised and their inhibitory activities evaluated against Plasmodium falciparum and Mycobacterium tuberculosis. In general, the hybrid complexes display good activity against the chloroquine-sensitive NF54 strain of P. falciparum. The neutral Ir(III)- and Rh(III)-Cp∗ complexes were the most active (IC50 = 0.488 μM for IrIII), maintaining activity against the multidrug-resistant K1 strain. Low to no cytotoxicity against the Chinese hamster ovarian cell line was observed for the tested complexes. Selected active hybrid complexes demonstrated significant inhibition of β-haematin formation in a cell-free NP-40 assay, suggesting an effect on the host haemoglobin degradation pathway as a potential contributing mechanism of action. When tested against M. tuberculosis H37Rv, most hybrid complexes displayed moderate to good activity. Again, the neutral complexes outperformed the cationic complexes, with the neutral Ir(III)-Cp∗ complexes proving most active (MIC90 = 0.488-1.490 μM).