Hydrosulfide Adducts of Organo-Iridium Anticancer Complexes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F16%3A33161200" target="_blank" >RIV/61989592:15310/16:33161200 - isvavai.cz</a>

Výsledek na webu

<a href="http://pubs.acs.org/doi/pdf/10.1021/acs.inorgchem.5b02697" target="_blank" >http://pubs.acs.org/doi/pdf/10.1021/acs.inorgchem.5b02697</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.inorgchem.5b02697" target="_blank" >10.1021/acs.inorgchem.5b02697</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Hydrosulfide Adducts of Organo-Iridium Anticancer Complexes

Popis výsledku v původním jazyce

Novel half-sandwich hydrosulfidoiridium(III) complexes [(eta(5)-Cp*)Ir(phen)(SH)]PF6 (1), [(eta(5)-Cp*)Ir(bpy)(SH)PF6 (2), [eta(5)-Cp-biph)Ir(phen)(SH)PF6 (3), and [(eta(5)-Cp-biph)Ir(bpy)(SH)PF6 (4) were prepared from the chlorido complexes by dechlorination and treatment with excess NaSH center dot xH(2)O; phen = 1,10-phenanthroline, bpy = 2,2'-bipyridine, Cp* = 1,2,3,4,5-pentamethylcyclopentadienyl, and Cp-biph = 1,2,3,4-tetramethyl-5-biphenylcyclopentadienyl. Complexes 1-4 were characterized by various techniques including electrospray ionization mass spectrometry, NMR spectroscopy (delta(SH) ca. -2 ppm), and a single-crystal X-ray analysis. Complex [eta(5)-Cp*)Ir(phen)(SH)]BPh4 (1') shows a typical piano-stool geometry with Ir-S bond length of 2.388(2) angstrom. Cp-biph complexes 3 (IC50 = 0.98 mu M) and 4 (IC50 = 0.61 mu M) showed significantly higher (p < 0.005) in vitro antiproliferative activity against A2780 human ovarian cancer cells, as compared with their Cp* analogues 1 (IC50 = 49.5 mu M) and 2 (IC50 = 48.4 mu M), and potency similar to the anticancer drug cisplatin. The complexes were relatively stable in aqueous solution toward hydrolysis and reactions with reduced glutathione (GSH), 9-ethylguanine, or 9-methyladenine. Interestingly, GSH was readily oxidized to glutathione disulfide in the presence of Cp-biph complexes 3 and 4, as judged by H-1 NMR, perhaps indicative of a possible redox-linked mechanism of action.

Název v anglickém jazyce

Hydrosulfide Adducts of Organo-Iridium Anticancer Complexes

Popis výsledku anglicky

Novel half-sandwich hydrosulfidoiridium(III) complexes [(eta(5)-Cp*)Ir(phen)(SH)]PF6 (1), [(eta(5)-Cp*)Ir(bpy)(SH)PF6 (2), [eta(5)-Cp-biph)Ir(phen)(SH)PF6 (3), and [(eta(5)-Cp-biph)Ir(bpy)(SH)PF6 (4) were prepared from the chlorido complexes by dechlorination and treatment with excess NaSH center dot xH(2)O; phen = 1,10-phenanthroline, bpy = 2,2'-bipyridine, Cp* = 1,2,3,4,5-pentamethylcyclopentadienyl, and Cp-biph = 1,2,3,4-tetramethyl-5-biphenylcyclopentadienyl. Complexes 1-4 were characterized by various techniques including electrospray ionization mass spectrometry, NMR spectroscopy (delta(SH) ca. -2 ppm), and a single-crystal X-ray analysis. Complex [eta(5)-Cp*)Ir(phen)(SH)]BPh4 (1') shows a typical piano-stool geometry with Ir-S bond length of 2.388(2) angstrom. Cp-biph complexes 3 (IC50 = 0.98 mu M) and 4 (IC50 = 0.61 mu M) showed significantly higher (p < 0.005) in vitro antiproliferative activity against A2780 human ovarian cancer cells, as compared with their Cp* analogues 1 (IC50 = 49.5 mu M) and 2 (IC50 = 48.4 mu M), and potency similar to the anticancer drug cisplatin. The complexes were relatively stable in aqueous solution toward hydrolysis and reactions with reduced glutathione (GSH), 9-ethylguanine, or 9-methyladenine. Interestingly, GSH was readily oxidized to glutathione disulfide in the presence of Cp-biph complexes 3 and 4, as judged by H-1 NMR, perhaps indicative of a possible redox-linked mechanism of action.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CA - Anorganická chemie

OECD FORD obor

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Projekt

<a href="/cs/project/LO1305" target="_blank" >LO1305: Rozvoj centra pokročilých technologií a materiálů</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Inorganic Chemistry

ISSN

0020-1669

e-ISSN

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Svazek periodika

55

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

8

Strana od-do

2324-2331

Kód UT WoS článku

000371753500042

EID výsledku v databázi Scopus

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