Synthesis, antimalarial activities and cytotoxicities of amino-artemisinin-1,2-disubstituted ferrocene hybrids

dc.contributor.authorDe Lange, Christo
dc.contributor.authorCoertzen, Dina
dc.contributor.authorSmit, Frans J.
dc.contributor.authorWentzel, Johannes F.
dc.contributor.authorWong, Ho Ning
dc.contributor.authorBirkholtz, Lyn-Marie
dc.contributor.authorHaynes, Richard K.
dc.contributor.authorN'Da, David D.
dc.date.accessioned2018-12-03T08:45:38Z
dc.date.issued2018-10
dc.description.abstractArtemisinin-ferrocene conjugates incorporating a 1,2-disubstituted ferrocene analogous to that embedded in ferroquine but attached via a piperazine linker to C10 of the artemisinin were prepared from the piperazine artemisinin derivative, and activities were evaluated against asexual blood stages of chloroquine (CQ) sensitive NF54 and CQ resistant K1 and W2 strains of Plasmodium falciparum (Pf). The most active was the morpholino derivative 5 with IC50 of 0.86 nM against Pf K1 and 1.4 nM against Pf W2. The resistance indices were superior to those of current clinical artemisinins. Notably, the compounds were active against Pf NF54 early and late blood stage gametocytes – these exerted >86% inhibition at 1 µM against both stages; they are thus appreciably more active than methylene blue (∼57% inhibition at 1 µM) against late stage gametocytes. The data portends transmission blocking activity. Cytotoxicity was determined against human embryonic kidney cells (Hek293), while human malignant melanoma cells (A375) were used to assess their antitumor activity.en_ZA
dc.description.departmentBiochemistryen_ZA
dc.description.departmentGeneticsen_ZA
dc.description.departmentMicrobiology and Plant Pathologyen_ZA
dc.description.embargo2019-10-15
dc.description.librarianhj2018en_ZA
dc.description.sponsorshipThe South African Medical Research Council (MRC) Flagship Project MALTB-Redox with funds from National Treasury under its Economic Competitiveness and Support Package and a South African National Research Foundation (NRF) Grant to R. K. Haynes (UID 90682).en_ZA
dc.description.urihttp://www.elsevier.com/ locate/bmclen_ZA
dc.identifier.citationDe Lange, C., Coertzen, D., Smit, F.J. et al. 2018, 'Synthesis, antimalarial activities and cytotoxicities of amino-artemisinin-1,2-disubstituted ferrocene hybrids', Bioorganic and Medicinal Chemistry Letters, vol. 28, no. 19, pp. 3161-3163.en_ZA
dc.identifier.issn0960-894X (print)
dc.identifier.issn1464-3405 (online)
dc.identifier.other10.1016/j.bmcl.2018.08.037
dc.identifier.urihttp://hdl.handle.net/2263/67429
dc.language.isoenen_ZA
dc.publisherElsevieren_ZA
dc.rights© 2018 Elsevier Ltd. All rights reserved. Notice : this is the author’s version of a work that was accepted for publication in Bioorganic and Medicinal Chemistry Letters. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. A definitive version was subsequently published in Bioorganic and Medicinal Chemistry Letters, vol. 28, no. 19, pp. 3161-3163, 2018. doi : 10.1016/j.bmcl.2018.08.037.en_ZA
dc.subjectAmino-artemisininen_ZA
dc.subjectCytotoxicityen_ZA
dc.subjectFerroceneen_ZA
dc.subjectHybrid drugen_ZA
dc.subjectMalariaen_ZA
dc.subjectArtemisinin based combination therapy (ACT)en_ZA
dc.titleSynthesis, antimalarial activities and cytotoxicities of amino-artemisinin-1,2-disubstituted ferrocene hybridsen_ZA
dc.typePostprint Articleen_ZA

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