Synthesis, spectral characterization, cytotoxicity and enzyme-inhibiting activity of new ferrocene–indole hybrids

Incorporation of a ferrocene moiety into the 2-phenylindole scaffold has been recently reported to drastically improve the cytotoxic activity of the parent compounds. In our search for new promising cytotoxic agents we designed and prepared two new ferrocene–indole hybrids, 2-(3-ferrocenylphenyl)-1H-indole and 2-(4-ferrocenylphenyl)-1H-indole, utilizing the Fischer indole synthesis as the key step. Detailed spectral analyses, including 1D and 2D NMR in various solvents, have been carried out to corroborate the structures of the synthesized compounds. In this work, we also present the first results of biological studies of these two compounds. Both compounds showed weak anticholinesterase activity but high cytotoxicity against rat peritoneal macrophages and the crustacean Artemia salina. Also, both compounds showed significant myeloperoxidase inhibiting activity, thus suggesting a potential use in inflammatory disorders. The results of these tests are very encouraging as they also suggest possible cytotoxic activities of these compounds against human cancer cell lines.

Two new ferrocene–indole hybrids were designed, synthesized and characterized by extensive 2D NMR studies. Although the compounds exerted weak inhibition of acetylcholinesterase, they demonstrated significant cytotoxic activities against Artemia salina (24 h LD50 20.7 and 120.4 μM) and rat macrophages (IC50 ca. 0.5 μM for both compounds).Figure optionsDownload as PowerPoint slide