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dc.contributor.authorHarmse, Rozanne
dc.contributor.authorSmit, Frans
dc.contributor.authorHaynes, Richard K.
dc.contributor.authorN'Da, David D.
dc.contributor.authorWong, Ho Ning
dc.date.accessioned2016-08-18T13:32:21Z
dc.date.available2016-08-18T13:32:21Z
dc.date.issued2015
dc.identifier.citationHarmse, R. et al. 2015. The case for development of 11-aza-artemisinins for malaria. Current medicinal chemistry, 22(31):3607-3630. [https://doi.org/10.2174/0929867322666150729115752]en_US
dc.identifier.issn1875-533X (Online)
dc.identifier.issn0929-8673
dc.identifier.urihttp://hdl.handle.net/10394/18322
dc.identifier.urihttp://www.eurekaselect.com/133573/article
dc.identifier.urihttps://doi.org/10.2174/0929867322666150729115752
dc.description.abstractThe current treatment regimens for uncomplicated malaria comprise an artemisinin in combination with another drug (ACT). However, the recent emergence of resistance to ACTs in South East Asia dramatically emphasizes the need for new artemisinins. The current artemisinins have been in use since the late 1970s and have relatively poor thermal, chemical and metabolic stabilities - all are metabolized or hydrolyzed in vivo to dihydroartemisinin (DHA) that itself undergoes facile decomposition in vivo. The current artemisinins possess neurotoxicity as demonstrated in animal models, an issue that mandates increased vigilance in view of trends to use of protracted treatment regimens involving sequential administration of different ACTs against the resistant disease. As artemisinins induce the most rapid reduction in parasitaemia of any drug, common sense dictates that any new artemisinin derivative, selected on the bases of more robust chemical and thermal stability, metabolic stability with respect to the generation of DHA in vivo, and relatively benign neurotoxicity should be used in any new ACT whose components are rationally chosen in order to counter resistant malaria and inhibit transmission. 11-Azaartemisinin and its N-substituted derivatives attract because of overall ease of preparation from artemisinin. Some derivatives also possess notable thermal stabilities and although metabolic pathways of the derivatives are as yet unknown, none can provide DHA. The azaartemisinins synthesized over the past 20 years are critically discussed on the basis of their synthetic accessibility and biological activities with the view to assessing suitability to serve as new artemisinin derivatives for treatment of malariaen_US
dc.language.isoenen_US
dc.publisherBentham Scienceen_US
dc.subjectArtemisininen_US
dc.subjectAzaartemisininen_US
dc.subjectDihydroartemisininen_US
dc.subjectMalariaen_US
dc.subjectMetabolismen_US
dc.subjectResistanceen_US
dc.subjectStabilityen_US
dc.titleThe case for development of 11-aza-artemisinins for malariaen_US
dc.typeArticleen_US
dc.contributor.researchID20547587 - Harmse, Rozanne
dc.contributor.researchID20926588 - Smit, Frans Johannes
dc.contributor.researchID22966390 - Haynes, Richard Kingston
dc.contributor.researchID20883072 - N'Da, David Dago
dc.contributor.researchID25904442 - Wong, Ho Ning


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