N-ferrocenylpyridazinones and new organic analogues

Synthesis, cyclic voltammetry, DFT analysis and in vitro antiproliferative activity associated with ROS-generation

Tamás Jernei, Sz. Bősze, Rita Szabó, F. Hudecz, Katalin Majrik, A. Csámpai

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Employing an optimized Pd-catalyzed cross-coupling reaction promoted by CuI, novel N-ferrocenylpyridazinones along with N-phenyl- and N-(2-pyridyl) analogues were synthesized from readily available heterocyclic precursors, iodoferrocene, iodobenzene and 2-bromopyridine. With exception of the ferrocenylation of 6-ferrocenylpyridazin-3(2H)-one yielding both N- and O-substituted products, the studied reactions exclusively afforded N-aryl lactams. The novel compounds exhibited cytotoxicity towards HEPG2 and HT-29 human malignant cells under in vitro conditions. The measured IC50 values supplemented with the results of cyclic voltammetry and DFT calculations suggest that the cytotoxic activity of the N- and O-ferrocenyl-substituted derivatives and the decreased effect of the N-phenyl analogues seem to be at least partly associated with the potential to generate reactive oxygen species (ROS). This interpretation, allowing the prediction of characteristic substituent-dependent SAR, was supported by the results of related studies on the practically inactive N-(2-pyridyl)pyridazinones assumed to be present in protonated chelate forms with highly a decreased propensity to undergo ionization.

Original languageEnglish
Pages (from-to)6181-6192
Number of pages12
JournalTetrahedron
Volume73
Issue number43
DOIs
Publication statusPublished - Jan 1 2017

Fingerprint

Synthetic Chemistry Techniques
Lactams
Cross Reactions
Cytotoxicity
Discrete Fourier transforms
Inhibitory Concentration 50
Cyclic voltammetry
Ionization
Reactive Oxygen Species
Derivatives
iodobenzene
In Vitro Techniques

Keywords

  • Cyclic voltammetry
  • Cytotoxicity
  • Ferrocene
  • HOMO energy
  • Ionization energy
  • Lactams
  • N-arylation
  • Pyridazine
  • SAR

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Cite this

N-ferrocenylpyridazinones and new organic analogues : Synthesis, cyclic voltammetry, DFT analysis and in vitro antiproliferative activity associated with ROS-generation. / Jernei, Tamás; Bősze, Sz.; Szabó, Rita; Hudecz, F.; Majrik, Katalin; Csámpai, A.

In: Tetrahedron, Vol. 73, No. 43, 01.01.2017, p. 6181-6192.

Research output: Contribution to journalArticle

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