Ferrocene-indole hybrids for cancer and malaria therapy

We report the synthesis, characterization, and cytotoxic and antimalarial activity of ferrocene-indole hybrids 8-14. The 2-phenylindole scaffold was chosen because of its potent antimitotic activity and ferrocene was chosen following the development of ferrocifens, ferrocene derivatives of tamoxifen, which are prototypes of a new family of organometallic anti-estrogens. Ferrocene-indole hybrids 8-14 and their corresponding organic analogues 1-7 showed only moderate antimalarial activities, while ferrocene-indole hybrids 11 and 12 showed excellent in vitro activities against the A549 human carcinoma cell line, with IC50 values of 5 and 7 mu M respectively. These ferrocene-indole hybrids were up to 25-fold more potent as cytotoxic agents than their purely organic analogues. (C) 2010 Elsevier B.V. All rights reserved.