Synthesis of artemiside and its effects in combination with conventional drugs against severe murine malaria
Language: 
English
Abstract: 

This research describes the use of novel antimalarial combinations of the new artemisinin derivative artemiside, a 10-alkylamino artemisinin. It is a stable, highly crystalline compound that is economically prepared from dihydroartemisinin in a one-step process. Artemiside activity was more pronounced than that of any antimalarial drug in use, both in Plasmodium falciparum culture and in vivo in a murine malaria model depicting cerebral malaria (CM). In vitro high-throughput testing of artemiside combinations revealed a large number of conventional antimalarial drugs with which it was additive. Following monotherapy in mice, individual drugs reduced parasitemias to nondetectable levels. However, after a period of latency, parasites again were seen and eventually all mice became terminally ill. Treatment with individual drugs did not prevent CM in mice with recrudescent malaria, except for piperaquine at high concentrations. Even when CM was prevented, the mice developed later of severe anemia. In contrast, most of the mice treated with drug combinations survived. A combination of artemiside and mefloquine or piperaquine may confer an optimal result because of the longer half life of both conventional drugs. The use of artemiside combinations revealed a significant safety margin of the effective artemiside doses. Likewise, a combination of 1.3 mg/kg of body weight artemiside and 10 mg/kg piperaquine administered for 3 days from the seventh day postinfection was completely curative. It appears possible to increase drug concentrations in the combination therapy without reaching toxic levels. Using the drug combinations as little as 1 day before the expected death of control animals, we could prevent further parasite development and death due to CM or anemic malaria. Earlier treatment may prevent cognitive dysfunctions which might occur after recovery from CM.

Author(s): 
Guo, Jin
Guiguemde, Armand W.
Bentura-Marciano, Annael
Clark, Julie
Haynes, Richard K.
Chan, Wing-Chi
Wong, Ho-Ning
Hunt, Nicholas H.
Guy, R. Kiplin
Golenser, Jacob
Item Type: 
Journal Article
Publication Title: 
Antimicrobial Agents and Chemotherapy
Journal Abbreviation: 
Antimicrob. Agents Chemother.
Publication Date: 
1/12/2015
Publication Year: 
2012
Pages: 
163-173
Volume: 
56
Issue: 
1
ISSN: 
1098-6596
DOI: 
10.1128/AAC.05006-11
Library Catalog: 
PubMed
Extra: 
PMID: 22006004 PMCID: PMC3256061

Turabian/Chicago Citation

Jin Guo, Armand W. Guiguemde, Annael Bentura-Marciano, Julie Clark, Richard K. Haynes, Wing-Chi Chan, Ho-Ning Wong, Nicholas H. Hunt, R. Kiplin Guy and Jacob Golenser. 1/12/2015. "Synthesis of artemiside and its effects in combination with conventional drugs against severe murine malaria." Antimicrobial Agents and Chemotherapy 56: 1: 163-173. 10.1128/AAC.05006-11.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1128/AAC.05006-11 | issn = 1098-6596 | volume = 56 | pages = 163-173 | last = Guo | first = Jin | coauthors = Guiguemde, Armand W., Bentura-Marciano, Annael, Clark, Julie, Haynes, Richard K., Chan, Wing-Chi, Wong, Ho-Ning, Hunt, Nicholas H., Guy, R. Kiplin, Golenser, Jacob | title = Synthesis of artemiside and its effects in combination with conventional drugs against severe murine malaria | journal = Antimicrobial Agents and Chemotherapy | date = 1/12/2015 | pmid = | pmc = }} </ref>