engleski

REDOX PROPERTIES, ROS GENERATION AND ANTIPROLIFERATIVE ACTIVITY OF FERROCENE-SUBSTITUTED NUCLEOBASES

Ferrocenyl compounds are shown to exhibit diverse biological activity through a redox mechanism by generating reactive oxygen species (ROS).[1] Since ferrocene-substituted nucleobases combine biogenic and redox-active parts, they have attracted the substantial attention and been investigated in medicinal chemistry to develop new candidates for therapeutic use.[2] To examine the biological activity of ferrocene-substituted nucleobases, we have prepared a series of ferrocene-substituted purine-nucleobase derivatives [3], measured their redox potential by the cyclic voltammetry and carried out an acellular ROS generation tests followed by in vitro cytotoxic studies on L929 and selected cancer cell lines. As expected, all measured compounds showed a reversible one-electron oxidation in the range of 300-450 mV with significant difference of approximately 100 mV between the N7 and N9 regioisomers allowing to easily distinguish them. The tendency of ferrocene-nucleobase conjugates to produce reactive oxygen species (ROS) was examined by DCFH assay in DMSO. The results showed that the nucleobases coupled with ferrocene generate ROS, while neither ferrocene itself nor the nucleobases were active. Finally, antiproliferative activity of compounds was examined using MTS viability assay of L929 cells and cancer cells HepG2 and Panc-1 to determine cytotoxic effect based on the IC50 values. Both the ability to produce acellular ROS as well as the IC50 are affected by the substituents on the purine ring.

Ferrocene, nucleobase, ROS, antiproliferative activity

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