An artificial alanine-based amino acid (TioxAla), bearing a substituted triazolyl-thione group on the side chain and able to bind RNA biomedical targets, was here chosen as a valuable scaffold for the synthesis of new platinum complexes with potential dual action owing to the concomitant presence of the metal centre and the amino acid moiety. Three new platinum complexes, obtained from the reaction of TioxAla with K2PtCl4, were characterized by mass spectrometry, NMR and UV–vis spectroscopy: one compound (Pt1) consisted of two amino acid units coordinating the Pt(II) ion; the other two, Pt2 and Pt3, were isomers including in their structure one TioxAla unit, and two chlorides as Pt-ligands. Pt coordination involved preferentially the amino, carboxylic and thione functions of TioxAla. By preliminary antiproliferative assays, a moderate cytotoxic activity on cancer cells was observed only for Pt2 and Pt3, and not for the chloride-free complex (Pt1), nor for TioxAla. This cytotoxicity, however lower than that of cisplatin, was connected with the marked ability, here found only for Pt2 and Pt3 complexes, to bind DNA sequences either in random coil or in structured forms (duplex and G-quadruplex), as verified by UV, CD and ESI-MS analysis.

Synthesis, DNA binding studies, and antiproliferative activity of novel Pt(II)-complexes with a L-alanyl-based ligand

Marzo, Tiziano;Pratesi, Alessandro;
2020-01-01

Abstract

An artificial alanine-based amino acid (TioxAla), bearing a substituted triazolyl-thione group on the side chain and able to bind RNA biomedical targets, was here chosen as a valuable scaffold for the synthesis of new platinum complexes with potential dual action owing to the concomitant presence of the metal centre and the amino acid moiety. Three new platinum complexes, obtained from the reaction of TioxAla with K2PtCl4, were characterized by mass spectrometry, NMR and UV–vis spectroscopy: one compound (Pt1) consisted of two amino acid units coordinating the Pt(II) ion; the other two, Pt2 and Pt3, were isomers including in their structure one TioxAla unit, and two chlorides as Pt-ligands. Pt coordination involved preferentially the amino, carboxylic and thione functions of TioxAla. By preliminary antiproliferative assays, a moderate cytotoxic activity on cancer cells was observed only for Pt2 and Pt3, and not for the chloride-free complex (Pt1), nor for TioxAla. This cytotoxicity, however lower than that of cisplatin, was connected with the marked ability, here found only for Pt2 and Pt3 complexes, to bind DNA sequences either in random coil or in structured forms (duplex and G-quadruplex), as verified by UV, CD and ESI-MS analysis.
2020
Riccardi, Claudia; Capasso, Domenica; Rozza, Giovanna M.; Platella, Chiara; Montesarchio, Daniela; Di Gaetano, Sonia; Marzo, Tiziano; Pratesi, Alessandro; Messori, Luigi; Roviello, Giovanni N.; Musumeci, Domenica
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/1011423
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