Investigation of new ferrocenyl-artesunate derivatives as antiparasitics.

Autor: Munnik BL; Department of Chemistry and Polymer Science, Stellenbosch University, Stellenbosch, Western Cape, South Africa. pchellan@sun.ac.za., Kaschula CH; Department of Chemistry and Polymer Science, Stellenbosch University, Stellenbosch, Western Cape, South Africa. pchellan@sun.ac.za., Harding CR; Wellcome Centre for Integrative Parasitology, Institute of Infection, Immunity and inflammation, University of Glasgow, UK., Chellan P; Department of Chemistry and Polymer Science, Stellenbosch University, Stellenbosch, Western Cape, South Africa. pchellan@sun.ac.za.
Jazyk: angličtina
Zdroj: Dalton transactions (Cambridge, England : 2003) [Dalton Trans] 2023 Nov 07; Vol. 52 (43), pp. 15786-15797. Date of Electronic Publication: 2023 Nov 07.
DOI: 10.1039/d3dt02254d
Abstrakt: Artesunate (Ars) is a semisynthetic antimalarial drug and is a part of the artemisinin-based combination therapy arsenal employed for malaria treatment. The drug functions mainly by activation of its endoperoxide bridge leading to increased oxidative stress in malaria parasites. The purpose of this study was to ascertain the antiparasitic effects of combining ferrocene and Ars via short or long chain ester or amide linkages (C1-C4). The compounds were evaluated for growth inhibition activity on the apicomplexan parasites, Plasmodium falciparum ( P. falciparum ) and Toxoplasma gondii ( T. gondii ). All the complexes demonstrated good activity against T. gondii with IC 50 values in the low micromolar range (0.28-1.2 μM) and good to excellent antimalarial activity against a chloroquine sensitive strain of P. falciparum (NF54). Further investigations on T. gondii revealed that the likely mode of action (MoA) is through the generation of reactive oxygen species. Additionally, immunofluorescence microscopy suggested a novel change in the morphology of the parasite by complex C3, an artesunate-ferrocenyl ethyl amide complex. The complexes were not cytotoxic or showed low cytotoxicity to two normal cell lines tested.
Databáze: MEDLINE
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