Peer-Reviewed Journal Details
Mandatory Fields
Mooney A.;Tiedt R.;Maghoub T.;O'Donovan N.;Crown J.;White B.;Kenny P.
2012
June
Journal of Medicinal Chemistry
Structure-activity relationship and mode of action of N-(6-ferrocenyl-2- naphthoyl) dipeptide ethyl esters: Novel organometallic anticancer compounds
Published
26 ()
Optional Fields
55
11
5455
5466
In this article, we report the findings of a comprehensive structure-activity relationship study of N-(6-ferrocenyl-2-naphthoyl) dipeptide ethyl esters, in which novel analogues were designed, synthesized, and evaluated in vitro for antiproliferative effect. Two new compounds, 2 and 16, showed potent nanomolar activity in the H1299 NSCLC cell line, with exceptional IC 50 values of 0.13 and 0.14 μM, respectively. These compounds were also found to have significant activity in the Sk-Mel-28 malignant melanoma cell line (IC 50 values of 1.10 and 1.06 μM, respectively). Studies were also conducted to elucidate the mode of action of these novel organometallic anticancer compounds. Cell cycle analysis in the H1299 cell line suggests these compounds induce apoptosis, while guanine oxidation studies confirm that 2 is capable of generating oxidative damage via a ROS-mediated mechanism. © 2012 American Chemical Society.
0022-2623
10.1021/jm3004027
Grant Details