engleski

Synthesis and biological evaluations of ferrocene- pyrimidine hybrids

Conjugation of organometallic fragments to a biologically active scaffold has been shown as an excellent strategy for improving the efficacy of drugs and reducing their toxicity. In this regard, ferrocene is a popular choice as bioisosteric group due to its stability and well-understood reactivity and electrochemistry [1]. In the search for bioorganometallic systems with an extended conjugation, our group's previous research has produced new ferrocenyl-nucleobase hybrids with a carbonyl bond between the heterocyclic and organometallic moieties. The synthesis of ferrocenoyl copulates is based on the acylation of nucleobase anions with ferrocenoyl chloride in DMF, where the ferrocenoylation reaction of pyrimidine bases is regiospecific and only the N1 product is formed [2]. However, in the case of purine derivatives, the substituents on the exocyclic amino group of adenine were shown to affect the reactivity of the corresponding purine anion and determine the regioselectivity of the reaction, leading to the formation of N7 and N9 isomers [3].In continuation of the research, a model reaction with uracil was performed to test the reaction regiospecificity in the formation of ferrocene-pyrimidine copulates (Figure 1). After optimizing the reaction conditions, we will focus on investigating the effects of substituents (electron donor or electron acceptor group) at the C-5 position of uracil on the formation of copulates. The position of the substitution in the products will be explored by spectroscopy methods. In order to evaluate the biological potential of synthesized compounds, their influence on specific immune response in mice was tested. The results suggest that examined compounds enhance the production of antigen-specific antibodies and have potential to be used in immune-mediated diseases.

ferrocene-pyrimidine hybrids

nije evidentirano