REAL

N-ferrocenylpyridazinones and new organic analogues: synthesis, cyclic voltammetry, DFT analysis and in vitro antiproliferative activity associated with ROS-generation

Jernei, Tamás and Bősze, Szilvia and Szabó, Rita and Hudecz, Ferenc and Majrik, Katalin and Csámpai, Antal (2017) N-ferrocenylpyridazinones and new organic analogues: synthesis, cyclic voltammetry, DFT analysis and in vitro antiproliferative activity associated with ROS-generation. TETRAHEDRON, 73. pp. 6181-6192. ISSN 0040-4020

[img] Text
Jernei_N_Fc_pyridazinones7.pdf - Accepted Version
Restricted to Registered users only until 13 September 2019.

Download (1MB)

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.

Item Type: Article
Subjects: Q Science / természettudomány > QD Chemistry / kémia > QD04 Organic chemistry / szerves kémia
Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3011 Biochemistry / biokémia
Depositing User: Dr Katalin Uray
Date Deposited: 13 Feb 2018 09:07
Last Modified: 13 Feb 2018 09:07
URI: http://real.mtak.hu/id/eprint/74294

Actions (login required)

Edit Item Edit Item