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dc.contributor.authorWu, Yuet
dc.contributor.authorWong, Ho Ning
dc.contributor.authorHaynes, Richard K.
dc.contributor.authorParapini, Silvia
dc.contributor.authorWilliams, Ian D.
dc.date.accessioned2018-10-11T09:49:10Z
dc.date.available2018-10-11T09:49:10Z
dc.date.issued2018
dc.identifier.citationWu, Y. et al. 2018. Facile preparation of N-glycosylated 10-piperazinyl artemisinin derivatives and evaluation of their antimalarial and cytotoxic activities. Molecules, 23: Article no 1713. [https://doi.org/10.3390/molecules23071713]en_US
dc.identifier.issn1420-3049 (Online)
dc.identifier.urihttp://hdl.handle.net/10394/31356
dc.identifier.urihttps://doi.org/10.3390/molecules23071713
dc.identifier.urihttps://www.mdpi.com/1420-3049/23/7/1713/pdf
dc.description.abstractAccording to the precepts that C-10 amino-artemisinins display optimum biological activities for the artemisinin drug class, and that attachment of a sugar enhances specificity of drug delivery, polarity and solubility so as to attenuate toxicity, we assessed the effects of attaching sugars to N-4 of the dihydroartemisinin (DHA)-piperazine derivative prepared in one step from DHA and piperazine. N-Glycosylated DHA-piperazine derivatives were obtained according to the Kotchetkov reaction by heating the DHA-piperazine with the sugar in a polar solvent. Structure of the D-glucose derivative is secured by X-ray crystallography. The D-galactose, L-rhamnose and D-xylose derivatives displayed IC50 values of 0.58–0.87 nM against different strains of Plasmodium falciparum (Pf) and selectivity indices (SI) >195, on average, with respect to the mouse fibroblast WEHI-164 cell line. These activities are higher than those of the amino-artemisinin, artemisone (IC50 0.9–1.1 nM). Notably, the D-glucose, D-maltose and D-ribose derivatives were the most active against the myelogenous leukemia K562 cell line with IC50 values of 0.78–0.87 µM and SI > 380 with respect to the human dermal fibroblasts (HDF). In comparison, artemisone has an IC50 of 0.26 µM, and a SI of 88 with the same cell lines. Overall, the N-glycosylated DHA-piperazine derivatives display antimalarial activities that are greatly superior to O-glycosides previously obtained from DHAen_US
dc.language.isoenen_US
dc.publisherMDPIen_US
dc.subjectArtemisininsen_US
dc.subjectArtemisoneen_US
dc.subjectPiperazineen_US
dc.subjectN-glycosidesen_US
dc.subjectAntimalarial activitiesen_US
dc.subjectAnti-tumour activitiesen_US
dc.titleFacile preparation of N-glycosylated 10-piperazinyl artemisinin derivatives and evaluation of their antimalarial and cytotoxic activitiesen_US
dc.typeArticleen_US
dc.contributor.researchID22966390 - Haynes, Richard Kingston
dc.contributor.researchID25904442 - Wong, Ho Ning


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