Use of anethole-type ligands to design cytotoxic organometallic ruthenium compounds: an experimental and computational study
Author
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Delgado, Ricardo
Author
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Galdámez Silva, Antonio
Author
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Tessini, Catherine
Author
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Ramírez Rivera, Sebastián
Author
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Aquea, Gisela
Author
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Bernal, Giuliano
Author
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Pinter, Balazs
Author
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Thomet, Franz
Admission date
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2020-04-23T14:10:47Z
Available date
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2020-04-23T14:10:47Z
Publication date
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2020
Cita de ítem
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Journal of Organometallic Chemistry 908 (2020) 121094
es_ES
Identifier
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0022-328X
Identifier
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10.1016/j.jorganchem.2019.121094
Identifier
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https://repositorio.uchile.cl/handle/2250/174063
Abstract
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Two hitherto unknown organometallic compounds with antitumor activity, [Ru(eta(6)-2-(1-propenyl)anisole)(en)(Cl)]PF6 (3) and [Ru(eta(6)-2-(1-propenyl)anisole)(en)(l)]PF6 (4), where en is ethylenediamine, were synthesized and completely characterized using standard techniques (H-1 and C-13 NMR, high-resolution MS and elemental analysis). The lipophilicity and hydrolysis rate kinetics were assessed and compared to the previously reported [Ru(eta(6)-4-(1-propenyl)anisole)(en)(halogen)]PF6 derivatives (4-(1-propenyl)anisole or anethole), where the halogen is Cl (1) or I (2). Based on the obtained rate constants, the coordination of (1-propenyl)anisole to the Ru(en) moiety yielded organometallic compounds that are as active as compounds that bind p-cymene as the arene ligand. Consistent with previously reported kinetic data, our density functional theory-based computational study revealed that an associative interchange mechanism predominates in the hydrolysis of this type of compound, and only small variations (similar to 1 kcal mol(-1)) were observed between the stabilities of the transition states corresponding to different derivatives. In vitro analyses of the anti-proliferative activity revealed that compounds 1 to 3 generally exhibit better cytotoxicity and selectivity (tumor versus non tumor cells) toward the gastric tumor cell lines AGS and SNU-1, compared to the parent [Ru(eta(6)-p-cymene)(en)X]PF6 (X: Cl and I) systems. Compound 3 showed similar cytotoxicity to compound 1 toward the AGS cell line, indicating that the change in the substitution pattern of the coordinated arene from 4-(1-propenyl)anisole to 2-(1-propenyl)anisole did not prominently affect the biological behavior. Compound 2 remained the most promising candidate to treat gastric cancer
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Patrocinador
dc.description.sponsorship
Universidad Tecnica Federico Santa Maria
DGIIP 116.13.1
CORFO
14IDL2-30087