Three new ferrocene complexes were synthesized with 4-(1H-pyrrol-1-yl)phenol group appended to one of the Cp ring. These are: 1,1′-4-(1H-pyrrol-1-yl)phenyl ferrocenedicarboxylate, ("Fc-(CO 2 -Ph-4-Py) 2 "), 1,4-(1H-pyrrol-1-yl)phenyl, 1′-carboxyl ferrocenecarboxylate ("Fc-(CO 2 -Ph-4-Py)CO 2 H") and 4-(1H-pyrrol-1-yl)phenyl ferroceneacetylate ("Fc-CH 2 CO 2 -Ph-4-Py"). The new species were characterized by standard analytical methods. Cyclic voltammetry experiments showed that Fc-CH 2 CO 2 -Ph-4-Py has redox potential very similar to the Fc/Fc + redox couple whereas Fc-(CO 2 -Ph-4-Py) 2 and Fc-(CO 2 -Ph-4-Py)CO 2 H have redox potentials of over 400 mV higher than Fc/Fc + redox couple. The in vitro studies on Fc-(CO 2 -Ph-4-Py) 2 and Fc-(CO 2 -Ph-4-Py)CO 2 H revealed that these two compounds have moderate anti-proliferative activity on MCF-7 breast cancer cell line. In contrast Fc-CH 2 CO 2 -Ph-4-Py which displayed low anti-proliferative activity. In the HT-29 colon cancer cell line, the new species showed low anti-proliferaive activity. Cytokinesis-block micronucleus assay (CBMN) was performed on these ferrocenes and it was determined they induce micronucleus formation on binucleated cells and moderate genotoxic effects on the MCF-7 breast cancer cell line. There is a correlation between the IC 50 values of the ferrocenes and the amount of micronucleus formation activity on binucleated cells and the reactive oxygen species (ROS) production on MCF-7 cell line.
Beta protein 1 (BP1) is a homeobox protein expressed in 80% of breast cancer cells in either estrogen receptor (ER) positive or ER negative breast cancer. However, it is barely detectable in normal breast tissues. In this project we present an electrochemical DNA nanostructured gold biosensor for detection of BP1. The gold sensor is first electrochemically nanostructured in 0.5 M sulfuric acid to reach superior conductivity, larger surface area, and higher stability. Nanostructured gold surface was characterized by atomic force microscopy (AFM) and scanning electron microscopy (SEM). The nanostructured gold sensor is then modified with double-stranded (ds) DNA mapping the genomic sequence that contains the binding site for BP1. A redox-active probe (methylene blue) was intercalated in dsDNA to monitor the binding event of BP1. A linear correlation of the electrochemical response by concentration of BP1 was obtained (R2 = 0.998) with a limit of detection of 1.2 nM. This nanostructured gold dsDNA sensor is shown to be sensitive, selective, stable, and reusable allowing for its potential clinical use.
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