Cymantrene, Cyrhetrene and Ferrocene Nucleobase Conjugates: Synthesis, Structure, Computational Study, Electrochemistry and Antitrypanosomal Activity

Konrad Kowalski, Lukasz Szczupk, Sebastian Saloman, Dietmar Steverding, Artur Jablonski, Valerije Vrcek, Alexander Hildebrandt, Heinrich Lang, Agnieszka Rybarczyk-Pirek

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Abstract

A series of cymantrene- and cyrhetrene-nucleobase derivatives together with the ferrocene-adenine conjugates have been prepared and characterized. The key step in synthesis of all compounds involved an N1-regioselective Michael addition of the respective nucleobase nucleophile to an in situ generated organometallic acryloyl electrophile reagent. The mechanism of this reaction was examined by DFT calculations. A single crystal X-ray diffraction study of cymantrene-adenine (5) were carried out and revealed that the plane of the adenine and the cyclopentadienyl group are almost perpendicular to each other. The cyclic voltammetry measurements on the cymantrenyl-nucleobases showed irreversible behavior for all compounds which can be explain by a ligand exchange of carbonyls with the donor functionality of the nucleobases. Cymantrene and cyrhetrene ketone nucleobases displayed significant in vitro activity against Trypanosoma brucei a causative parasite of sleeping sickness. They showed no cytotoxicity against human HL-60 cancer cells.
Original languageEnglish
Pages (from-to)303-314
Number of pages12
JournalChemPlusChem
Volume82
Issue number2
Early online date5 Oct 2016
DOIs
Publication statusPublished - 7 Feb 2017

Keywords

  • bioorganometalic chemistry
  • cymantrene
  • cyrhetrene
  • ferrocene
  • nucleobases
  • antitrypanosomal activity

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