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Issue 59, 2015
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In vitro antimalarial activity and molecular modeling studies of novel artemisinin derivatives

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Abstract

Cerebral malaria is a serious and sometimes fatal disease caused by a Plasmodium falciparum parasite that infects a female anopheles mosquito which feeds on humans. The parasites responsible for mosquito-borne infectious diseases are increasingly resistant to current drug approaches, and almost half of the world is at risk of contracting an illness. A series of twenty five new ether and ester derivatives of dihydroartemisinin (DHA) have been prepared based on in silico studies and in vitro antimalarial activity and later assessed against the chloroquine sensitive NF-54 strain of Plasmodium falciparum. In general the incorporation of nitro functionality in ester derivatives enhances the activity relative to artemisinin. Most of the ether derivatives were found to be as active as DHA, while 11-OH ether derivatives were not as active as DHA. The most potent analogue in the series was compound 21 which was several fold more active than artemisinin against P. falciparum used in the study. Molecular docking and ADMET studies were performed to explore the possible mode of interaction of active compounds in to the binding site pocket of malaria parasite target enzyme plasmepsin-II and evaluated compliance with oral bioavailability and pharmacokinetics parameters. The ester derivatives 19 and 20 were found to be twice active than DHA, having nitro functionality showing IC50 10.58 nM and 8.54 nM respectively.

Graphical abstract: In vitro antimalarial activity and molecular modeling studies of novel artemisinin derivatives

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Publication details

The article was received on 27 Apr 2015, accepted on 20 May 2015 and first published on 21 May 2015


Article type: Paper
DOI: 10.1039/C5RA07697H
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RSC Adv., 2015,5, 47959-47974

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    In vitro antimalarial activity and molecular modeling studies of novel artemisinin derivatives

    R. Gaur, H. S. Cheema, Y. Kumar, S. P. Singh, D. K. Yadav, M. P. Darokar, F. Khan and R. S. Bhakuni, RSC Adv., 2015, 5, 47959
    DOI: 10.1039/C5RA07697H

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