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Enantioselective Cytotoxicity of Chiral Diphosphine Ruthenium(II) Complexes Against Cancer Cells

The chiral cationic complex [Ru(η(1)‐OAc)(CO)((R,R)‐Skewphos)(phen)]OAc (2 ( R )), isolated from reaction of [Ru(η(1)‐OAc)(η(2)‐OAc)(R,R)‐Skewphos)(CO)] (1 ( R )) with phen, reacts with NaOPiv and KSAc affording [RuX(CO)((R,R)‐Skewphos)(phen)]Y (X=Y=OPiv 3 ( R ); X=SAc, Y=OAc 4 ( R )). The correspon...

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Detalles Bibliográficos
Autores principales: Lovison, Denise, Alessi, Dario, Allegri, Lorenzo, Baldan, Federica, Ballico, Maurizio, Damante, Giuseppe, Galasso, Marilisa, Guardavaccaro, Daniele, Ruggieri, Silvia, Melchior, Andrea, Veclani, Daniele, Nardon, Chiara, Baratta, Walter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9322675/
https://www.ncbi.nlm.nih.gov/pubmed/35394095
http://dx.doi.org/10.1002/chem.202200200
Descripción
Sumario:The chiral cationic complex [Ru(η(1)‐OAc)(CO)((R,R)‐Skewphos)(phen)]OAc (2 ( R )), isolated from reaction of [Ru(η(1)‐OAc)(η(2)‐OAc)(R,R)‐Skewphos)(CO)] (1 ( R )) with phen, reacts with NaOPiv and KSAc affording [RuX(CO)((R,R)‐Skewphos)(phen)]Y (X=Y=OPiv 3 ( R ); X=SAc, Y=OAc 4 ( R )). The corresponding enantiomers 2 ( S )‐4 ( S ) have been obtained from 1 ( S ) containing (S,S)‐Skewphos. Reaction of 2 ( R ) and 2 ( S ) with (S)‐cysteine and NaPF(6) at pH=9 gives the diastereoisomers [Ru((S)‐Cys)(CO)(PP)(phen)]PF(6) (PP=(R,R)‐Skewphos 2 ( R )‐Cys; (S,S)‐Skewphos 2 ( S )‐Cys). The DFT energetic profile for 2 ( R ) with (S)‐cysteine in H(2)O indicates that aquo and hydroxo species are involved in formation of 2 ( R )‐Cys. The stability of the ruthenium complexes in 0.9 % w/v NaCl solution, PBS and complete DMEM medium, as well as their n‐octanol/water partition coefficient (logP), have been evaluated. The chiral complexes show high cytotoxic activity against SW1736, 8505 C, HCT‐116 and A549 cell lines with EC(50) values of 2.8–0.04 μM. The (R,R)‐Skewphos derivatives show higher cytotoxicity compared to their enantiomers, 4 ( R ) (EC(50)=0.04 μM) being 14 times more cytotoxic than 4 ( S ) against the anaplastic thyroid cancer 8505 C cell line.