dc.contributor.author | Wu, Yuet | |
dc.contributor.author | Wong, Ho Ning | |
dc.contributor.author | Haynes, Richard K. | |
dc.contributor.author | Parapini, Silvia | |
dc.contributor.author | Williams, Ian D. | |
dc.date.accessioned | 2018-10-11T09:49:10Z | |
dc.date.available | 2018-10-11T09:49:10Z | |
dc.date.issued | 2018 | |
dc.identifier.citation | Wu, Y. et al. 2018. Facile preparation of N-glycosylated 10-piperazinyl artemisinin derivatives and evaluation of their antimalarial and cytotoxic activities. Molecules, 23: # 1713. [https://doi.org/10.3390/molecules23071713] | en_US |
dc.identifier.issn | 1420-3049 (Online) | |
dc.identifier.uri | http://hdl.handle.net/10394/31356 | |
dc.identifier.uri | https://www.mdpi.com/1420-3049/23/7/1713/pdf | |
dc.identifier.uri | https://doi.org/10.3390/molecules23071713 | |
dc.description.abstract | According 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 DHA | en_US |
dc.language.iso | en | en_US |
dc.publisher | MDPI | en_US |
dc.subject | Artemisinins | en_US |
dc.subject | Artemisone | en_US |
dc.subject | Piperazine | en_US |
dc.subject | N-glycosides | en_US |
dc.subject | Antimalarial activities | en_US |
dc.subject | Anti-tumour activities | en_US |
dc.title | Facile preparation of N-glycosylated 10-piperazinyl artemisinin derivatives and evaluation of their antimalarial and cytotoxic activities | en_US |
dc.type | Article | en_US |
dc.contributor.researchID | 22966390 - Haynes, Richard Kingston | |
dc.contributor.researchID | 25904442 - Wong, Ho Ning | |