2,3-Dihydroimidazo[1,2-b]ferroceno[d]pyridazines and a 3,4-dihydro-2H- pyrimido[1,2-b]ferroceno[d]pyridazine

Synthesis, structure and in vitro antiproliferation activity on selected human cancer cell lines

Dániel Csókás, Benedek I. Károlyi, Sz. Bősze, Ildikó Szabó, Gábor Báti, L. Drahos, A. Csámpai

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Starting from (Sp)-ferroceno[d]pyridazin-1(2H)-one a series of novel ferrocene-fused heterocycles with planar- and central chirality were synthesised. The thione analogue of the precursor obtained by treatment with Lawesson reagent underwent facile mercury-mediated aminations with a selection of aminoalcohols. The resulted intermediates were subjected to cyclisations by Appel- and Mitsunobu protocols. Two diastereomers carrying phenyl group in endo- and exo positions, respectively, in the fused metallocene scaffold underwent spontaneous oxidation affording the same planar chiral imidazo[1,2-b] ferroceno[d]pyridazine isolated as side product. The structures of the new compounds including diastereomers of different central chirality were confirmed by IR, 1H, 13C and 15N NMR spectroscopy. The in vitro antitumour activity of the fused ferrocene derivatives was investigated against HepG2 hepatoma and HT-29 colorectal adenocarcinoma cell cultures by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-assay. The measured 50% inhibitory concentration (IC50) values indicate that synthesised metallocene bases can be regarded as lead structures for the development of a novel class of heavy metal-free drug candidates with promising activity.

Original languageEnglish
Pages (from-to)41-48
Number of pages8
JournalJournal of Organometallic Chemistry
Volume750
DOIs
Publication statusPublished - 2014

Fingerprint

Pyridazines
2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulfide
Chirality
chirality
cultured cells
Inhibitory Concentration 50
cancer
Cells
Thiones
Amination
Cell Line
Cyclization
synthesis
heavy metals
Heavy Metals
Mercury
Cell culture
Scaffolds
Nuclear magnetic resonance spectroscopy
Heavy metals

Keywords

  • Anticancer activity
  • Central chirality
  • DFT modelling
  • Fused ferrocene
  • NMR spectroscopy
  • Pyridazine planar chirality

ASJC Scopus subject areas

  • Inorganic Chemistry
  • Organic Chemistry
  • Physical and Theoretical Chemistry
  • Materials Chemistry
  • Biochemistry

Cite this

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title = "2,3-Dihydroimidazo[1,2-b]ferroceno[d]pyridazines and a 3,4-dihydro-2H- pyrimido[1,2-b]ferroceno[d]pyridazine: Synthesis, structure and in vitro antiproliferation activity on selected human cancer cell lines",
abstract = "Starting from (Sp)-ferroceno[d]pyridazin-1(2H)-one a series of novel ferrocene-fused heterocycles with planar- and central chirality were synthesised. The thione analogue of the precursor obtained by treatment with Lawesson reagent underwent facile mercury-mediated aminations with a selection of aminoalcohols. The resulted intermediates were subjected to cyclisations by Appel- and Mitsunobu protocols. Two diastereomers carrying phenyl group in endo- and exo positions, respectively, in the fused metallocene scaffold underwent spontaneous oxidation affording the same planar chiral imidazo[1,2-b] ferroceno[d]pyridazine isolated as side product. The structures of the new compounds including diastereomers of different central chirality were confirmed by IR, 1H, 13C and 15N NMR spectroscopy. The in vitro antitumour activity of the fused ferrocene derivatives was investigated against HepG2 hepatoma and HT-29 colorectal adenocarcinoma cell cultures by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-assay. The measured 50{\%} inhibitory concentration (IC50) values indicate that synthesised metallocene bases can be regarded as lead structures for the development of a novel class of heavy metal-free drug candidates with promising activity.",
keywords = "Anticancer activity, Central chirality, DFT modelling, Fused ferrocene, NMR spectroscopy, Pyridazine planar chirality",
author = "D{\'a}niel Cs{\'o}k{\'a}s and K{\'a}rolyi, {Benedek I.} and Sz. Bősze and Ildik{\'o} Szab{\'o} and G{\'a}bor B{\'a}ti and L. Drahos and A. Cs{\'a}mpai",
year = "2014",
doi = "10.1016/j.jorganchem.2013.10.057",
language = "English",
volume = "750",
pages = "41--48",
journal = "Journal of Organometallic Chemistry",
issn = "0022-328X",
publisher = "Elsevier",

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TY - JOUR

T1 - 2,3-Dihydroimidazo[1,2-b]ferroceno[d]pyridazines and a 3,4-dihydro-2H- pyrimido[1,2-b]ferroceno[d]pyridazine

T2 - Synthesis, structure and in vitro antiproliferation activity on selected human cancer cell lines

AU - Csókás, Dániel

AU - Károlyi, Benedek I.

AU - Bősze, Sz.

AU - Szabó, Ildikó

AU - Báti, Gábor

AU - Drahos, L.

AU - Csámpai, A.

PY - 2014

Y1 - 2014

N2 - Starting from (Sp)-ferroceno[d]pyridazin-1(2H)-one a series of novel ferrocene-fused heterocycles with planar- and central chirality were synthesised. The thione analogue of the precursor obtained by treatment with Lawesson reagent underwent facile mercury-mediated aminations with a selection of aminoalcohols. The resulted intermediates were subjected to cyclisations by Appel- and Mitsunobu protocols. Two diastereomers carrying phenyl group in endo- and exo positions, respectively, in the fused metallocene scaffold underwent spontaneous oxidation affording the same planar chiral imidazo[1,2-b] ferroceno[d]pyridazine isolated as side product. The structures of the new compounds including diastereomers of different central chirality were confirmed by IR, 1H, 13C and 15N NMR spectroscopy. The in vitro antitumour activity of the fused ferrocene derivatives was investigated against HepG2 hepatoma and HT-29 colorectal adenocarcinoma cell cultures by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-assay. The measured 50% inhibitory concentration (IC50) values indicate that synthesised metallocene bases can be regarded as lead structures for the development of a novel class of heavy metal-free drug candidates with promising activity.

AB - Starting from (Sp)-ferroceno[d]pyridazin-1(2H)-one a series of novel ferrocene-fused heterocycles with planar- and central chirality were synthesised. The thione analogue of the precursor obtained by treatment with Lawesson reagent underwent facile mercury-mediated aminations with a selection of aminoalcohols. The resulted intermediates were subjected to cyclisations by Appel- and Mitsunobu protocols. Two diastereomers carrying phenyl group in endo- and exo positions, respectively, in the fused metallocene scaffold underwent spontaneous oxidation affording the same planar chiral imidazo[1,2-b] ferroceno[d]pyridazine isolated as side product. The structures of the new compounds including diastereomers of different central chirality were confirmed by IR, 1H, 13C and 15N NMR spectroscopy. The in vitro antitumour activity of the fused ferrocene derivatives was investigated against HepG2 hepatoma and HT-29 colorectal adenocarcinoma cell cultures by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-assay. The measured 50% inhibitory concentration (IC50) values indicate that synthesised metallocene bases can be regarded as lead structures for the development of a novel class of heavy metal-free drug candidates with promising activity.

KW - Anticancer activity

KW - Central chirality

KW - DFT modelling

KW - Fused ferrocene

KW - NMR spectroscopy

KW - Pyridazine planar chirality

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U2 - 10.1016/j.jorganchem.2013.10.057

DO - 10.1016/j.jorganchem.2013.10.057

M3 - Article

VL - 750

SP - 41

EP - 48

JO - Journal of Organometallic Chemistry

JF - Journal of Organometallic Chemistry

SN - 0022-328X

ER -