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JAC Advance Access published online on November 18, 2002
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg008
© 2002 by The British Society for Antimicrobial Chemotherapy
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© 2002 The British Society for Antimicrobial Chemotherapy

Original Paper

Activity against Plasmodium falciparum of cycloperoxide compounds obtained from the sponge Plakortis simplex

Ernesto Fattorusso 1, Silvia Parapini 2, Claudio Campagnuolo 1, Nicoletta Basilico 2, Orazio Taglialatela-Scafati 1, Donatella Taramelli 2*

1 Dipartimento di Chimica delle Sostanze Naturali, Università di Napoli ‘Federico II', via D. Montesano 49, I-80131 Napoli, Italy
2 Istituto di Microbiologia, Università degli Studi di Milano, Via Pascal 36, 20133 Milano, Italy

* Corresponding author. E-mail: donatella.taramelli{at}unimi.it.

Received 8 February 2002 ; revised 24 June 2002 ; accepted 22 September 2002

Abstract

There is an urgent need to discover new antimalarials, due to the spread of chloroquine resistance and the limited number of available drugs. In the last few years, artemisinin, the endoperoxide sesquiterpene lactone derived from Artemisia annua, and its derivatives proved to be very active against Plasmodium falciparum. These compounds are characterized by an endoperoxide pharmacophore that is critical for their antimalarial activity. There are several reports, from our group and others, that marine organisms can be another natural source of stable cyclic peroxides, with selective antifungal or antibacterial activity. With the aim of identifying new bioactive molecules, we evaluated in vitro the antimalarial activity of the major cycloperoxides extracted from the sponge Plakortis simplex. The six-membered endoperoxide compounds plakortin and dihydroplakortin, but not the five-membered cycloperoxide plakortide E, inhibited the growth of cultured P. falciparum parasites, both chloroquine-sensitive D10 strain and chloroquine-resistant W2 strain. The IC50 values were similar for both compounds and in the range of 1263-1117 nM against D10, and 735-760 nM against W2, using the colorimetric parasite lactate dehydrogenase assay. The activity of plakortin and dihydroplakortin was significantly higher against chloroquine-resistant than chloroquine-susceptible parasites, following a pattern similar to that of artemisinin, although they were 50-fold less active. Moreover, plakortin and dihydroplakortin showed an additive effect when used in combination with chloroquine. These results support further studies on cycloperoxides of marine origin to characterize their mechanism of action and identify/synthesize new compounds with stronger antimalarial activity.

Keywords: P. falciparum, artemisinin, chloroquine, peroxides, marine metabolites, antimalarials
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