Assessment of the Nematocidal Activity of Metallocenyl Derivatives of Monepantel

Content Provider	Semantic Scholar
Author	Hess, Jeannine Patra, Malay Jabbar, Abdul Pierroz, Vanessa Sandro Konatschnig Spingler, Bernhard Ferrari, Stefano Gasserb, Robin B. Gilles Gassera
Copyright Year	2017
Abstract	In this study, we present the design, synthesis, characterization and biological evaluation of structurally new ferrocenyl and ruthenocenyl derivatives of the recently launched organic anthelmintic monepantel (Zolvix). All seven metallocenyl derivatives prepared (4a/b, 5a/b, 6a/b and 7) were isolated as racemates and characterized by H, C and F NMR spectroscopies, mass spectrometry, IR spectroscopy and microanalysis. The molecular structures of four compounds (4a/b, 6a and 7) were further confirmed by X-ray crystallography. The biological activities of the organometallic-intermediates (4a/b) and organometallic-derivatives of monepantel (5a/b, 6a/b and 7) were evaluated in vitro using parasitic nematodes of major importance in livestock, namely Haemonchus contortus and Trichostrongylus colubriformis. Two ferrocenyl compounds (4a and 6a) showed nematocidal activity, while the analogous ruthenocenyl compounds (4b and 6b) were not active at the highest concentration tested (10 μg/mL). In order to obtain insight into the difference in activity of ferrocenyl and ruthenocenyl derivatives, the potential of the compounds for reactive oxidative species (ROS) production in living cells was assessed. Interestingly, neither the ferrocenyl nor the ruthenocenyl compounds (4a/b and 6a/b) produced significant ROS in HeLa cells, indicating a redox-independent activity of 4a and 6a on parasites. The selectivity of the compounds towards parasites was further confirmed through the investigation of the cytotoxic profile of all the compounds. All of them were found to be non-toxic either to HeLa or to MRC-5 cell lines. Thus, 4a and 6a could be considered as interesting leads for further development of new classes of anti-parasitic agents.
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Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article