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Synthesis of bioconjugates of ferrocene and pyrimidine nucleobases and chemosensitivity of human lung epithelial cells

Nucleosides and their analogs have a significant role in drug discovery and development due to their remarkable chemotherapeutic activities. In these drug molecules the sugar unit frequently modified (e.g. in AZT or gemcitabine) or completely replaced (e.g. in abacavir and acyclovir).1 The thio analogs of pyrimidine bases, including their S-, N-, or S, N-disubstituted analogs, have shown therapeutic properties, especially antiviral, antithyroid, and antitumor activities.2 On the other side, studies of various ferrocene derivatives indicate that cancer cell cytotoxicity derives from oxidation to the ferrocenium ion, facilitating the generation of reactive-oxygen species (ROS) which, in turn, inflict damage upon the genetic material, thereby inducing apoptosis. For synthesis of nucleoside derivatives, the N- alkylation reaction of nucleobases is often achieved with different sources of carbon electrophiles. However, the nucleobase reactivity is often altered by their reduced nucleophilicity and the increased acidity of the NH groups.1The replacement of the sugar molecular fragment of nucleosides by a redox- active, metal-containing ferrocenyl moiety could give an access to electron-conducting, self-organizing polymers with applications in biology, medicine, and nanotechnology.3 We now report the synthesis of hybrids in which ferrocene and uracil/thiouracil moieties are linked through carbonyl units (Fig. 1). Chemosensitivity pattern of human lung epithelial cells (A549) to bioconjugates of ferrocene and uracil/thiouracil derivative was determined by tetrazolium assay (MTS) and IC50 was determined for all compounds. Though the exact mechanism of the observed chemosensitivity of human epithelial lung cells to applied conjugates needs to be elucidated, noticed effect of different derivatives on cells shows path for development of new potential drugs.

uracil-ferrocene conjugates, thiouracil-ferrocene conjugates, chemosensitivity, human lung epithelial cells

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