Browsing by Author "Jordaan, Lydia"

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    The synthesis and evaluation of new organometallic benzimidazole Complexes as antiplasmodials
    (Stellenbosch : Stellenbosch University, 2020, 2020-12) Jordaan, Lydia; Chellan, Prinessa; Stellenbosch University. Faculty of Science. Dept. of Chemistry and Polymer Science.
    ENGLISH ABSTRACT: Despite ongoing efforts to discover new antimalarial drugs, malaria remains a serious concern in developing countries due to the widespread resistance of Plasmodium falciparum (P. falciparum) to antimalarial drugs such as chloroquine. Organometallic complexes, particularly those containing platinum group metals have shown great promise for the development of new antimalarial treatments. The majority of antiplasmodial organometallic complexes reported in the literature are derived from quinoline-containing ligands. Benzimidazole is an attractive pharmacophore as it has displayed various pharmacological activities and can bind to a range of biological receptors. Few organometallic complexes of benzimidazoles have been reported, and even fewer that display antimalarial activity. In this study, two known and four new cationic iridium and rhodium complexes were synthesised from 2-(2-pyridyl)benzimidazole and metal dimers with different η5-Cpx groups (x = Me, ph or biph). Six new neutral cyclometallated iridium and rhodium complexes of 2- phenylbenzimidazole were also synthesised, as several C^N cyclometallated complexes reported in the literature have displayed improved biological activities compared to their N^N analogues. All complexes were obtained in moderate to good yields with high purity. The complexes were characterised using infrared and 1H and 13C NMR spectroscopy as well as mass spectrometry. The single crystal X-ray structures of the pyridyl complexes were obtained and confirmed the expected molecular structures. The pyridyl (C1 – C6) and phenyl complexes (C7 – C12) all displayed moderate to good antiplasmodial activity against the CQ-sensitive 3D7 strain of P. falciparum. The pyridyl complexes were also evaluated against the CQ-resistant Dd2 strain and, in general, improved activities were observed compared to 3D7. In general, the rhodium complexes out-performed the iridium complexes in both series and an increase in activity was observed when the cyclopentadienyl group was extended, in the order Cp* < Cpxph < Cpxbiph. This can be attributed to increased hydrophobicity. The cyclometallated rhodium Cpxbiph complex, which is the most active of the cyclometallated complexes, deviates from this trend. The pyridyl complexes exhibited low cytotoxicity to human embryonic kidney (HEK) cells compared to their activity against P. falciparum strains, which is an indication of good selectivity. Future work will involve investigating potential mechanism of action of these complexes, performing further in vitro biological tests on the cyclometallated complexes and potentially modifying the ligand to improve the antimalarial activities of these complexes. Overall, the newly synthesised pyridyl and cyclometallated organometallic complexes are promising candidates for further investigation as potential antimalarial agents.