6343-19-7Relevant academic research and scientific papers
Synthesis, biological evaluation and SAR studies of novel bicyclic antitumor platinum(IV) complexes
Lorenzo, Julia,Delgado, Aida,Monta?a, ángel M.,Mesas, Juan M.,Alegre, María-Teresa,Rodríguez, María Del Carmen,Avilés, Francesc-Xavier
, p. 374 - 388 (2014)
The present study describes the synthesis, anticancer activity and SAR studies of novel platinum(IV) complexes having 1,2-bis(aminomethyl)carbobicyclic or oxabicyclic carrier ligands, bearing chlorido and/or hydroxido ligands in axial position and chlorido or malonato ligands in equatorial position (labile ligands). These complexes were synthetized with the aim of obtaining new anticancer principles more soluble in water and therefore more bioavailable. Several substitution patterns on the platinum atom have been designed in order to evaluate their antiproliferative activity and to establish structure-activity relationship rules. The synthesis of platinum(IV) complexes with axial hydroxyl ligands on the platinum(IV) were carried out by reaction of K 2Pt(OH)2Cl4 with the corresponding diamines. The complexes with axial chlorido ligands on the platinum(IV) atom were synthesized by direct reaction of diamines with K2PtCl6. Carboxylated complexes were synthesized by the substitution reaction of equatorial chlorido ligands by silver dicarboxylates. The most actives complexes were those having malonate as a labile ligand, no matter of the structure of the carrier ligand. Regarding the influence of the structure of the non-labile 1,4-diamine carrier ligand on the cytotoxicity, it was found that the complexes having the more lipophilic and symmetrical bicyclo[2.2.2]octane framework were much more active than those having an oxygen or methylene bridge.
Synthesis, biophysical studies, and antiproliferative activity of platinum(II) complexes having 1,2-bis(aminomethyl)carbobicyclic ligands
De Mier-Vinué, Jordi,Gay, Marina,Monta?a, ángel M.,Sáez, Rosa-Isabel,Moreno, Virtudes,Kasparkova, Jana,Vrana, Oldrich,Heringova, Pavla,Brabec, Viktor,Boccarelli, Angela,Coluccia, Mauro,Natile, Giovanni
, p. 424 - 431 (2008/09/19)
A selected chemical library of six platinum(II) complexes having 1,2-bis(aminomethyl)carbobicyclic ligands were synthesized after a rational design in order to evaluate their antiproliferative activity and the structure-activity relationships. The cytotoxicity studies were performed using cancer cell lines sensitive (A2780) and resistant (A2780R) to cisplatin. Excellent cytotoxicity was observed for most of complexes, which presented better resistance factors than cisplatin against the A2780R cell line. The interaction of these complexes with DNA, as the target biomolecule, was evaluated by several methods: DNA-platinum binding kinetics, changes in the DNA melting temperature, evaluation of the unwinding angle of supercoiled DNA, evaluation of the interstrand cross-links, and replication mapping. The kinetics of the interaction with glutathione was also investigated to better understand the resistant factors observed for the new complexes.
