Bimodal X-ray and Infrared Imaging of an Organometallic Derivative of Praziquantel in Schistosoma mansoni

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Bimodal X-ray and Infrared Imaging of an Organometallic Derivative of Praziquantel in Schistosoma mansoni, ChemBioChem 2016, 17, 1-5


The neglected parasitic tropical disease schistosomiasis, which is also known as bilharzia, affects more than 249 million people worldwide. The majority of infections occur in schoolaged children. The disease is triggered by parasitic worms (schistosomes) with a complex life cycle. Five species of schistosomes, primarily Schistosoma haematobium, S. japonicum, and S. mansoni, and, in some regions, S. intercalatum and S. mekongi, are responsible for human infections leading either to intestinal or urogenital schistosomiasis. The only drug available to date to treat this disease is the organic compound praziquantel (PZQ). PZQ is administered orally as a racemic mixture, although only the R enantiomer has antihelmintic activity. Surprisingly, although PZQ has been approved since the early 1980s and millions of doses are administered to patients worldwide each year (42.1 million people were treated in 2012), its mode of action remains primarily unknown. There is evidence that PZQ alters the function of voltage-operated calcium channels (VOCC) through a unique channel bsubunit. However, this assumption is under debate, as discussed in a recent review by Cupit and Cunningham. Another hypothesis is that PZQ interacts with tegumental phospholipids, this was supported recently by using MS imaging. Nonetheless, unveiling the mode of action of PZQ would be highly significant in view of the discovery of novel antischistosomal drug candidates. The proposed targets are located in the tegument, and knowing the location of PZQ in the worm body would thus be informative.



In conclusion, we have described, for the first time, a correlative imaging study using two synchrotron-based imaging techniques to locate an organometallic drug candidate in a biological context, specifically in the cryosections of a parasite. This innovative approach allowed us not only to unambiguously detect metal–CO derivatives of the antischistosomal drug PZQ in worms but also to prove the integrity of the M(CO)3 core after incubation. An organometallic derivative of PZQ, 1, which is believed to share some biological targets with the parent PZQ, showed accumulation in the worm tegument when administered at concentrations of 100 and 500 mm. This study, aimed at determining the topology of the distribution of 1 in worms, contributes to the understanding of the target of PZQ and might help, in conjunction with other studies, to decipher the mode of action of this antischistosomal drug, which is still under debate. On a more general note, this work is also a strong encouragement for the use of organometallic compounds in medicinal chemistry, as it not only allows for the potential discovery of novel drug candidates but, very importantly, presents an opportunity to apply new emerging analytical techniques to answer questions about the location of administered organometallic compounds. Overall, this could provide additional information to help resolve modes of action.


N'hésitez pas également à consulter le communiqué de presse associé à cet article : Suivre l’action d’un traitement antiparasitaire




ChemBioChem 2016, 17, 1-5


An organometallic derivative of praziquantel was studied directly in worms by using inductively coupled plasma-mass spectrometry (ICP-MS) for quantification and synchrotronbased imaging. X-ray fluorescence (XRF) and IR absorption spectromicroscopy were used for the first time in combination to directly locate this organometallic drug candidate in schistosomes. The detection of both CO (IR) and Cr (XRF) signatures proved that the Cr(CO)3 core remained intact in the worms. Images showed a preferential accumulation at the worm’s tegument, consistent with a possible targeting of the calcium channel but not excluding other biological targets inside the worm.

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Bimodal X-ray and Infrared Imaging of an Organometallic Derivative of Praziquantel in Schistosoma mansoni


Dr. Sylvain Clède, Noemi Cowan, Dr. François Lambert, Dr. Hélène C. Bertrand, Dr. Riccardo Rubbiani, Dr. Malay Patra, Jeannine Hess, Dr. Christophe Sandt, Dr. Nicolas Trcera, Prof. Dr. Gilles Gasser5, Prof. Dr. Jennifer Keiser and Prof. Dr. Clotilde Policar


ChemBioChem 2016, 17, 1-5


doi: 10.1002/cbic.201500688