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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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 by1H,13C, and19F 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 parasites Haemonchus contortus and Trichostrongylus colubriformis. Moderate nematocidal activity was observed for nine of the 27 compounds. Three compounds were confirmed as potentiators of a known monepantel target, the ACR-23 ion channel. Production of reactive oxygen species may confer secondary activity to the organometallic analogues. Two compounds, namely, an organic precursor (3 a) and a cymantrene analogue (9 a), showed activities against microfilariae of Dirofilaria immitis in the low microgram per milliliter range.

Original languageEnglish
Pages (from-to)16602-16612
Number of pages11
JournalChemistry - A European Journal
Issue number46
StatePublished - 7 Nov 2016
Externally publishedYes


  • anthelmintics
  • bioorganometallic chemistry
  • drug design
  • medicinal chemistry
  • metallocenes


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