Journal
ACTA TROPICA
Volume 89, Issue 3, Pages 329-342Publisher
ELSEVIER
DOI: 10.1016/j.actatropica.2003.10.006
Keywords
artemisinin; semi-synthetic derivatives; structurally simplified trioxanes; molecular mechanism(s) of action
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Artemisinin and simplified trioxane analogs constitute a promising class of antimalarial chemotherapeutic agents. Their development since the early 1970s into clinical trials and clinical use has drawn much attention from medical scientists worldwide although the crude extract containing artemisinin has been used in China for treatment of fever for many centuries. Many research groups have independently and collaboratively conducted various studies on the artemisinin system both in search for the new compounds more antimalarially active than the parent artemisinin and in an attempt to understand its molecular mechanism(s) of action. Ongoing studies have provided a better understanding of the putative intermediates essential for the antimalarial activity and have led to designer trioxanes whose chemical structures have been simplified and modified to increase efficacy while lowering toxicity. Other desirable features beneficial to clinical uses such as bioavailability, drug stability and water solubility have been considered, and portions of the trioxane skeleton have been added or modified to accommodate these parameters accordingly. (C) 2003 Elsevier B.V. All rights reserved.
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