Synthesis, Structural Characterization and Antitrypanosomal Activity of Ferrocenyl-Based Imines with 2 or 4)-Nitrophenyl-2-Furan Group

Two new metallocene complexes with formulation [Fe(η5-C<inf>5</inf>H<inf>5</inf>){(η5-C<inf>5</inf>H<inf>4</inf>)-N[dbnd]CH-2-C<inf>4</inf>H<inf>2</inf>O-(5-C<inf>6</inf>H<inf>4</inf>-2-NO<inf>2</inf>)}] (3) and [Fe(η5-C<inf>5</inf>H<inf>5</inf>){(η5-C<inf>5</inf>H<inf>4</inf>)-N[dbnd]CH-2-C<inf>4</inf>H<inf>2</inf>O-(5-C<inf>6</inf>H<inf>4</inf>-4-NO<inf>2</inf>)}] (4) have been synthesized and their antitrypanosomal activity has been evaluated. Complexes 3 and 4 were obtained by condensation reaction of ferrocenylamine (1) with respective 5-(2-nitrophenyl)-2-furancarboxaldehyde (2a) or 5-(4-nitrophenyl)-2-furancarboxaldehyde (2b). The complexes were fully characterized by spectroscopic techniques (FT-IR, 1H and 13C{1H} NMR, and HRMS), which confirm their correct obtainment. The crystal structures of 3 and 4 were also determined by single crystal X-ray diffraction. Furthermore, UV–visible studies revealed that compounds 3 and 4 exhibited suitable stability in DMSO:HEPES buffer solution (80:20) throughout 24 h. The in vitro antiparasitic activities of ferrocenyl imine derivatives 3 and 4 were assessed against two species of parasites, Trypanosoma cruzi (T. cruzi) and Trypanosoma brucei (T. brucei). The obtained results revealed that compound 3 (EC<inf>50</inf> = 0.44 μM) exhibited nearly a 40-fold greater efficacy as an anti-T. brucei agent compared to derivative 4 (EC<inf>50</inf> = 16.0 μM). Moreover, compound 3 demonstrated superior potency when compared with its organometallic analogs (EC<inf>50</inf> = 2.42–13.3 μM), which were previously reported by our research group. Interestingly, the EC<inf>50</inf> value of 3 was found to be 8 times greater than that of nifurtimox (EC<inf>50</inf> = 3.56 μM). The cytotoxicity of the ferrocenyl imines was also evaluated on the L<inf>6</inf> rat skeletal myoblast cell line. © 2024 Elsevier B.V.