Res. Chem. Intermed.
, Vol. 30, No. 6, pp. 615–625 (2004)
Also available online - www.vsppub.com
Free radicals formed by addition of antimalaric
artemisinin (Qinghaosu, QHS) to human serum:
an ESR-spin trapping investigation
, DANTE MACCIANTELLI
and GIANCARLO MARCONI
ISOF, Area della Ricerca del CNR, Via P. Gobetti 101, I-40129 Bologna, Italy
Received 28 January 2004; accepted 4 March 2004
Abstract—The antimalaric drug artemisinin (QHS) is believed to operate through a mechanism
initiated with the cleavage of its endoperoxidic bond induced by transition metal ions. An ESR
investigation of the reaction of QHS with human serum in the presence of two spin trapping agents
has led to the detection of spin adducts of carbon-centred radicals. Experiments carried out replacing
the human serum with iron(II) salts led to the observation of the same spin adducts, thus supporting
previous suggestions that also in vivo the drug operates via a radical-based mechanism. UV irradiation
of QHS also led to the trapping of transient free radicals.
Keywords: Artemisinin; ESR; spin trapping.
Malaria represents one of the most dangerous diseases in many tropical and
subtropical areas, as more than 500 million people are infected annually and it
is estimated that every 12 s one person dies due to the consequences of this
infection . Unfortunately, the traditional drugs employed to ﬁght malaria (i.e.
chloroquine and meﬂoquine) are becoming less and less effective, due to the
rapid resistance developed by the major agent of the most pernicious form of
this infection, i.e. the Plasmodium falciparum protozoon . With the aim to
overcome this problem a new class of antimalaric drugs has been devised, the
activity of which is based on a completely different principle. The prototype of
these drugs is Artemisinin (QHS, 1), a cyclic trioxane containing an endoperoxidic
bond that is isolated from Artemisia annua L., a herb widely used in the ancient
To whom correspondence should be addressed. E-mail: email@example.com or firstname.lastname@example.org