Ferrocenyl Derivatives of the Anthelmintic Praziquantel: Design, Synthesis, and Biological Evaluation

The design, synthesis, and biological evaluation of 18
ferrocenyl
derivatives (4A–12A and 4B–12B) of the most well-known drug against schistosomiasis,
namely praziquantel (PZQ), are reported. These compounds, which have
been all isolated as racemates, were unambiguously characterized by 1H and 13C NMR spectroscopy, mass spectrometry,
and elemental analysis as well as by X-ray crystallography for 4A, 5A, and 7A. Cytotoxicity studies
revealed that the complexes were moderately toxic toward a cervical
cancer cell line (HeLa) and, importantly, significantly less active
toward a noncancerous cell line (MRC-5). The in vitro anthelmintic activity of the 18 ferrocenyl PZQ derivatives was tested
against adult Schistosoma mansoni, and values in
the micromolar range (26–68 μM) were determined for the
four most active compounds. It was also demonstrated using two compounds
of the series as models (8A and 8B) that
the complexes were stable when incubated for 24 h at 37 °C in
human plasma.