Investigation of the molecular reactivity of bioactive oxiranylmethyloxy anthraquinones.
Giovanni RibaudoAlberto OngaroMaira ZorzanRaffaele PezzaniMarco RedaelliGiuseppe ZagottoMaurizio MemoAlessandra GianoncelliPublished in: Archiv der Pharmazie (2019)
The design of a multitarget and multifunctional small molecule containing two functional groups reacting through different mechanisms represents an attractive goal for the medicinal chemist. The preparation of two bifunctional oxiranylmethyloxy anthraquinones, previously investigated as anticancer agents, is described here. These compounds combine a planar, DNA-intercalating and pro-oxidant anthraquinone scaffold and the alkylating epoxide functions which can covalently react with the nucleic acid. Their multilevel molecular reactivity was studied through a combination of analytical techniques: The DNA-binding properties were investigated using a mass spectrometry-based binding assay and by nuclear magnetic resonance, highlighting the formation of a covalent adduct with a nucleobase. Moreover, the contribution of the pro-oxidant redox cycling was evaluated.
Keyphrases
- dna binding
- nucleic acid
- anti inflammatory
- small molecule
- magnetic resonance
- mass spectrometry
- transcription factor
- single molecule
- liquid chromatography
- atomic force microscopy
- drug delivery
- high throughput
- high resolution
- cancer therapy
- high intensity
- magnetic resonance imaging
- circulating tumor
- contrast enhanced
- high performance liquid chromatography
- gas chromatography
- electron transfer