Loading...
Thumbnail Image
Item

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

Baartzes, N.
Jordaan, A.
Warner, D.F.
Combrinck, J.
Taylor, D.
Chibale, K.
Smith, G.S.
Abstract
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).
Description
Date
2020-11-15
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Research Projects
Organizational Units
Journal Issue
Keywords
Aminoquinolines , Antimicrobial , Benzimidazoles , Bioorganometallic chemistry , Hybrids , Platinum group metals
Citation
Baartzes N, Jordaan A, Warner DF, Combrinck J, Taylor D, Chibale K, Smith GS. Antimicrobial evaluation of neutral and cationic iridium(III) and rhodium(III) aminoquinoline-benzimidazole hybrid complexes. European Journal of Medicinal Chemistry. 2020;206:112694. DOI: https://doi.org/10.1016/j.ejmech.2020.112694.
Embedded videos