Synthesis, characterization and antitumor activity of 1,2-disubstituted ferrocenes and cyclodextrin inclusion complexes

Seven different ferrocene derivatives have been tested in vitro against Ehrlich ascites tumor cells. Neither ferrocene nor the monosubstituted derivative N, N-dimethylaminomethylferrocene showed cytotoxic activity (IC(50) > 1000 mu M for 3 h treatments). Better results were obtained with 1,2-disubstituted derivatives. The IC(50) values ranged from 376.6 mu M for 1,2-diformylferrocene to 71.2 mu M for racemic 2-( N, N-dimethylaminomethyl) ferrocenecarboxamide. The latter derivative was also encapsulated in native beta-cyclodextrin ( CD), heptakis-2,3, 6-tri-O-methyl-beta-CD (TRIMEB) and 2-hydroxypropyl-beta-CD (HP beta CD) to give 1: 1 (host: guest) inclusion compounds. The existence of true inclusion complexes in the solid state was confirmed by a combination of powder X-ray diffraction, thermogravimetric analysis, FTIR and (13)C CP MAS NMR spectroscopy. The IC(50) value for the beta-CD inclusion compound was identical to that obtained for the nonincluded ferrocene derivative. By contrast, the inclusion compounds comprising TRIMEB and HP beta CD yielded IC(50) values of 25.2 and 20.0 mu M, respectively. No obvious relationship could be established between the redox behavior of the compounds determined by cyclic voltammetry and the biochemical data. (c) 2007 Elsevier B. V. All rights reserved.