REAL

Synthesis and anticancer activity studies of ferrocenyl-thymine-3,6-dihydro-2H-thiopyranes – a new class of metallocene-nucleobase derivatives

Skiba, Joanna and Karpowicz, Rafał and Szabó, Ildikó and Therrien, Bruno and Kowalski, Konrad (2015) Synthesis and anticancer activity studies of ferrocenyl-thymine-3,6-dihydro-2H-thiopyranes – a new class of metallocene-nucleobase derivatives. Journal of Organometallic Chemistry, 794. pp. 216-222. ISSN 0022-328X

[img] Text
Skiba_J.Organomet.Chem_2015.pdf - Published Version
Restricted to Repository staff only

Download (990kB)

Abstract

A convenient synthesis of ferrocenyl-4-thiothymine-3,6-dihydro-2H-thiopyrane (3) and ferrocenyl-thymine-3,6-dihydro-2H-thiopyrane (4) by a hetero-Diels-Alder cycloaddition reaction is reported. These complexes represent new class of ferrocenyl nucleobase derivatives. The 2H-thiopyrane ring mimics the sugar subunit present in natural nucleosides and nucleotides. The X-ray crystal structure analysis of the precursor thioketone (1) showed that individual molecules of 1 form H-bonded dimers in the solid state. Compounds 3 and 4 were tested in vitro for their antiproliferative activity against human colon carcinoma HT-29, estrogen receptor-responsive human breast adenocarcinoma MCF-7, estrogen-negative human breast adenocarcinoma MDA-MB-231, human promyelocytic leukemia HL-60 and human monocytic MonoMac6 cancer cells. Ferrocenyl-4-thiothymine-3,6-dihydro-2H-thiopyrane 3 showed a cytostatic effect on MonoMac6, MCF-7 and HL-60 cell lines, but was devoid of activity on MDA-MB-231 and HT-29 cells. In contrast, all cell lines tested were sensitive toward thymine derivative 4. Proapoptic activity of 3 and 4 was confirmed by means of acridine orange/ethidium bromide (AO/EB) double-staining assay.

Item Type: Article
Uncontrolled Keywords: Bioorganometallics, Ferrocene, Thioketones, Cycloaddition, Anticancer activity
Subjects: Q Science / természettudomány > QD Chemistry / kémia > QD04 Organic chemistry / szerves kémia
Q Science / természettudomány > QP Physiology / élettan
Depositing User: Dr Katalin Uray
Date Deposited: 28 Oct 2015 11:26
Last Modified: 28 Oct 2015 11:26
URI: http://real.mtak.hu/id/eprint/29965

Actions (login required)

Edit Item Edit Item