Improving cytotoxic properties of ferrocenes by incorporation
of saturated N-heterocycles

J 2017

Improving cytotoxic properties of ferrocenes by incorporation of saturated N-heterocycles

HODÍK, Tomáš, Martin LAMAČ, Lucie Červenková ŠŤASTNÁ, Petra CUŘÍNOVÁ, Jindřich KARBAN et. al.

Basic information

Original name

Improving cytotoxic properties of ferrocenes by incorporation of saturated N-heterocycles

Authors

HODÍK, Tomáš, Martin LAMAČ, Lucie Červenková ŠŤASTNÁ, Petra CUŘÍNOVÁ, Jindřich KARBAN, Hana SKOUPILOVÁ, Roman HRSTKA, Ivana CÍSAŘOVÁ, Róbert GYEPES and Jiří PINKAS

Edition

Journal of Organometallic Chemistry, Lausanne, Elsevier Science, 2017, 0022-328X

Other information

Type of outcome

Článek v odborném periodiku

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 1.946

Keywords (in Czech)

Kovové sloučeniny, deriváty ferocenu, N-heterocykly, cytotoxicita, rakovina vaječníků

Keywords in English

Metallodrugs, Ferrocene derivatives, N-heterocycles, Cytotoxicity, Ovarian cancer

Abstract

V originále

A family of ferrocene derivatives of the general formula [Fe(h5-C5H4CH2(p-C6H4)CH2(N-het))2] bearing saturated six- and five-membered N-heterocycles (N-het) was prepared. Reactions of the selected complexes with acids (HCl, acetic acid) afforded either the corresponding hydrochlorides or led to deprotection of the functionalized pendant N-heterocycles. The reaction of [{Ru(h6-p-cymene)Cl2}2] with the corresponding cyclopentadienide derivatives afforded cationic ruthenium complexes [Ru(h6-pcymene)( h5-C5H4CH2(p-C6H4)CH2(N-het))]Cl while ruthenocenes [Ru(h5-C5H4CH2(p-C6H4)CH2(N-het))2] were formed as minor byproducts. The prepared complexes (20 examples) were characterized by elemental analysis, melting point, NMR and ESI-MS and the molecular structures of selected ferrocene derivatives were determined by X-ray diffraction analysis. The ferrocene derivatives and the ruthenium complexes were tested in vitro for their cytotoxic properties against three cell lines derived from ovarian cancer (A2780, A2780cis, and SK-OV-3) and against non-tumour embryonic cell line HEK293 (human kidney cells). The most active ferrocene derivatives displayed cytotoxicity in submicromolar and low micromolar concentration against both cisplatin (CisPt) sensitive and resistant cells. The results showed a significant effect of the pendant N-heterocycle on the ferrocene derivative toxicity and selectivity against cancer cells. Ultimately, ferrocene derivatives bearing either piperidine or morpholine groups were proposed to be the most promising substitutes for platinum drugs, as they exhibited comparable or even higher activity (in comparison to CisPt) against cancer cells, whereas these compounds were found to exhibit lower toxicity against embryonic HEK293 cells.

Citovat

HODÍK, Tomáš, Martin LAMAČ, Lucie Červenková ŠŤASTNÁ, Petra CUŘÍNOVÁ, Jindřich KARBAN, Hana SKOUPILOVÁ, Roman HRSTKA, Ivana CÍSAŘOVÁ, Róbert GYEPES and Jiří PINKAS. Improving cytotoxic properties of ferrocenes by incorporation of saturated N-heterocycles. Journal of Organometallic Chemistry. Lausanne: Elsevier Science, 2017, vol. 2017, No 846, p. 141–151. ISSN 0022-328X.

@article{1390161,
   author = {Hodík, Tomáš and Lamač, Martin and Šťastná, Lucie Červenková and Cuřínová, Petra and Karban, Jindřich and Skoupilová, Hana and Hrstka, Roman and Císařová, Ivana and Gyepes, Róbert and Pinkas, Jiří},
   article_location = {Lausanne},
   article_number = {846},
   keywords = {Metallodrugs, Ferrocene derivatives, N-heterocycles, Cytotoxicity, Ovarian cancer},
   issn = {0022-328X},
   journal = {Journal of Organometallic Chemistry},
   title = {Improving cytotoxic properties of ferrocenes by incorporation of saturated N-heterocycles},
   volume = {2017},
   year = {2017}
}

TY  - JOUR
ID  - 1390161
AU  - Hodík, Tomáš - Lamač, Martin - Šťastná, Lucie Červenková - Cuřínová, Petra - Karban, Jindřich - Skoupilová, Hana - Hrstka, Roman - Císařová, Ivana - Gyepes, Róbert - Pinkas, Jiří
PY  - 2017
TI  - Improving cytotoxic properties of ferrocenes by incorporation of saturated N-heterocycles
JF  - Journal of Organometallic Chemistry
VL  - 2017
IS  - 846
SP  - 141–151
EP  - 141–151
PB  - Elsevier Science
SN  - 0022328X
KW  - Metallodrugs, Ferrocene derivatives, N-heterocycles, Cytotoxicity, Ovarian cancer
N2  - A family of ferrocene derivatives of the general formula [Fe(h5-C5H4CH2(p-C6H4)CH2(N-het))2] bearing saturated six- and five-membered N-heterocycles (N-het) was prepared. Reactions of the selected complexes with acids (HCl, acetic acid) afforded either the corresponding hydrochlorides or led to deprotection of the functionalized pendant N-heterocycles. The reaction of [{Ru(h6-p-cymene)Cl2}2] with the corresponding cyclopentadienide derivatives afforded cationic ruthenium complexes [Ru(h6-pcymene)( h5-C5H4CH2(p-C6H4)CH2(N-het))]Cl while ruthenocenes [Ru(h5-C5H4CH2(p-C6H4)CH2(N-het))2] were formed as minor byproducts. The prepared complexes (20 examples) were characterized by elemental analysis, melting point, NMR and ESI-MS and the molecular structures of selected ferrocene derivatives were determined by X-ray diffraction analysis. The ferrocene derivatives and the ruthenium complexes were tested in vitro for their cytotoxic properties against three cell lines derived from ovarian cancer (A2780, A2780cis, and SK-OV-3) and against non-tumour embryonic cell line HEK293 (human kidney cells). The most active ferrocene derivatives displayed cytotoxicity in submicromolar and low micromolar concentration against both cisplatin (CisPt) sensitive and resistant cells. The results showed a significant effect of the pendant N-heterocycle on the ferrocene derivative toxicity and selectivity against cancer cells. Ultimately, ferrocene derivatives bearing either piperidine or morpholine groups were proposed to be the most promising substitutes for platinum drugs, as they exhibited comparable or even higher activity (in comparison to CisPt) against cancer cells, whereas these compounds were found to exhibit lower toxicity against embryonic HEK293 cells.
ER  -

HODÍK, Tomáš, Martin LAMAČ, Lucie Červenková ŠŤASTNÁ, Petra CUŘÍNOVÁ, Jindřich KARBAN, Hana SKOUPILOVÁ, Roman HRSTKA, Ivana CÍSAŘOVÁ, Róbert GYEPES and Jiří PINKAS. Improving cytotoxic properties of ferrocenes by incorporation of saturated N-heterocycles. \textit{Journal of Organometallic Chemistry}. Lausanne: Elsevier Science, 2017, vol.~2017, No~846, p.~141–151. ISSN~0022-328X.

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