Straightforward conversion of decoquinate into inexpensive tractable new derivatives with significant antimalarial activities

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dc.contributor.author Beteck, Richard M.
dc.contributor.author Coertzen, Dina
dc.contributor.author Smit, Frans J.
dc.contributor.author Birkholtz, Lyn-Marie
dc.contributor.author Haynes, Richard K.
dc.contributor.author N’Da, David D.
dc.date.accessioned 2016-07-04T06:31:18Z
dc.date.issued 2016-07
dc.description.abstract As part of a programme aimed at identifying rational new triple drug combinations for treatment of malaria, tuberculosis and toxoplasmosis, we have selected quinolones as one component, given that selected examples exhibit exceptionally good activities against the causative pathogens of the foregoing diseases. The quinolone decoquinate (DQ), an old and inexpensive coccidiostat, displays anti-malarial activity in vitro against Plasmodium falciparum (Pf). However, because of its exceedingly poor solubility in water or organic solvents, development of DQ as a drug is problematical. We have therefore converted DQ in straightforward fashion into tractable new derivatives that display good activities in vitro against chloroquine-sensitive NF54 and multidrug-resistant K1 and W2 Pf, and relatively low toxicities against human fibroblast cells. The most active compound, the N-acetyl derivative 30, is 5-fold more active than DQ against NF54 and K1 and equipotent with DQ against W2. It possesses an activity profile against all strains comparable with that of the artemisinin derivative artesunate. Overall, this compound and the other accessible and active derivatives serve as an attractive template for development of new and economic lead quinolones. en_ZA
dc.description.department Biochemistry en_ZA
dc.description.embargo 2017-07-31
dc.description.librarian hb2016 en_ZA
dc.description.sponsorship This research project is funded by the South African Medical Research Council (MRC) with funds from the National Treasury under its Economic Competitiveness and Support Package. The South African National Research Foundation is thanked for financial support to LMB (UID 84627) and RKH (Grant No. 90682). en_ZA
dc.description.uri http://www.elsevier.com/locate/bmcl en_ZA
dc.identifier.citation Beteck, RM, Coertzen, D, Smit, FJ, Birkholtz, L-M, Haynes, RK & N'Da, DD 2016, 'Straightforward conversion of decoquinate into inexpensive tractable new derivatives with significant antimalarial activities', Bioorganic and Medicinal Chemistry Letters, vol. 26, no. 13, pp. 3006-3009. en_ZA
dc.identifier.issn 0968-0896 (print)
dc.identifier.issn 1464-3391 (online)
dc.identifier.other 10.1016/j.bmcl.2016.05.024
dc.identifier.uri http://hdl.handle.net/2263/53594
dc.language.iso en en_ZA
dc.publisher Elsevier en_ZA
dc.rights © 2016 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. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Bioorganic and Medicinal Chemistry Letters, vol. 26, no. 13, pp. 3006-3009, 2016. doi : 10.1016/j.bmcl.2016.05.024. en_ZA
dc.subject Malaria en_ZA
dc.subject Quinolone en_ZA
dc.subject Decoquinate en_ZA
dc.subject Derivatives en_ZA
dc.subject Antimalarial activity en_ZA
dc.subject Quinolone decoquinate (DQ) en_ZA
dc.subject Plasmodium falciparum (Pf) en_ZA
dc.title Straightforward conversion of decoquinate into inexpensive tractable new derivatives with significant antimalarial activities en_ZA
dc.type Postprint Article en_ZA


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