Journal article

Organometallic Derivatization of the Nematocidal Drug Monepantel Leads to Promising Antiparasitic Drug Candidates

Jeannine Hess, Malay Patra, Loganathan Rangasamy, Sandro Konatschnig, Olivier Blacque, Abdul Jabbar, Patrick Mac, Erik M Jorgensen, Robin B Gasser, Gilles Gasser

CHEMISTRY-A EUROPEAN JOURNAL | WILEY-V C H VERLAG GMBH | Published : 2016

Abstract

The discovery of novel drugs against animal parasites is in high demand due to drug-resistance problems encountered around the world. Herein, the synthesis and characterization of 27 organic and organometallic derivatives of the recently launched nematocidal drug monepantel (Zolvix® ) are described. The compounds were isolated as racemates and were characterized by 1 H, 13 C, and 19 F NMR spectroscopy, mass spectrometry, and IR spectroscopy, and their purity was verified by microanalysis. The molecular structures of nine compounds were confirmed by X-ray crystallography. The anthelmintic activity of the newly designed analogues was evaluated in vitro against the economically important parasi..

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Grants

Awarded by Swiss National Science Foundation


Awarded by US National Institutes of Health (NINDS)


Funding Acknowledgements

This work was financially supported by the Swiss National Science Foundation (Professorships No PP00P2_133568 and PP00P2_157545 to G.G.), the University of Zurich (G.G.), the Stiftung fur wissenschaftliche Forschung of the University of Zurich (G.G.), the Novartis Jubilee Foundation (G.G), and the Swiss Government Excellence Scholarship for Postdoctoral Researcher (R.L.). R.B.G.'s research program is supported by the Australian Research Council (ARC), the National Health and Medical Research Council (NHMRC), Melbourne Water Corporation, Yourgene Bioscience, the Alexander von Humboldt Foundation, and The University of Melbourne. E.M.J. is supported by the US National Institutes of Health (NINDS R01-NS034307) and is an Investigator of the Howard Hughes Medical Institute (HHMI). R.B.G. and E.M.J. are grateful recipients of Professorial Humboldt Research Awards. The authors would like to thank Dr. Jacques Bouvier (Novartis Animal Health, St-Aubin, Switzerland) and Dr. Noelle Gauvry (Novartis Animal Health, Basel, Switzerland) for their help with the biological assays.