1. Synthesis, DNA binding studies, and antiproliferative activity of novel Pt(II)-complexes with an L-alanyl-based ligand
- Author
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Domenica Capasso, Luigi Messori, Daniela Montesarchio, Tiziano Marzo, Chiara Platella, Claudia Riccardi, Domenica Musumeci, Alessandro Pratesi, Giovanna M. Rozza, Sonia Di Gaetano, Giovanni N. Roviello, Riccardi, C., Capasso, D., Rozza, G. M., Platella, C., Montesarchio, D., Di Gaetano, S., Marzo, T., Pratesi, A., Messori, L., Roviello, G. N., and Musumeci, D.
- Subjects
Stereochemistry ,ESI-MS spectrometry ,chemistry.chemical_element ,Antineoplastic Agents ,010402 general chemistry ,Ligands ,01 natural sciences ,Biochemistry ,Inorganic Chemistry ,Metal ,chemistry.chemical_compound ,NMR spectroscopy ,Coordination Complexes ,Cell Line, Tumor ,Side chain ,Moiety ,Humans ,DNA binding ,Platinum ,chemistry.chemical_classification ,Alanine ,010405 organic chemistry ,CD spectroscopy ,Nuclear magnetic resonance spectroscopy ,DNA ,0104 chemical sciences ,Amino acid ,G-Quadruplexes ,Pt(II)-complexes ,Triazolyl-thione L-alanine ligand ,Propanoic acid ,chemistry ,visual_art ,triazolyl-thione L-alanine ligand ,visual_art.visual_art_medium ,Drug Screening Assays, Antitumor ,Pt(II)-complexe - Abstract
An artificial alanine-based amino acid {(S)-2-amino-3-[4-propyl-3-(thiophen-2-yl)-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]propanoic acid, here named 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, nuclear magnetic resonance and UV–vis spectroscopy: one compound (Pt1, bis-{(S)-2-amino-3-[4-propyl-3-(thiophen-2-yl)-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]propanoate-O,S} platinum(II)) consisted of two amino acid units coordinating the Pt(II) ion; the other two, Pt2 [potassium dichloro-{(S)-2-amino-3-[4-propyl-3-(thiophen-2-yl)-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]propanoate (O,S)} platinum(II)] and Pt3 [potassium dichloro-{(S)-2-amino-3-[4-propyl-3-(thiophen-2-yl)-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]propanoate (O,N)} platinum(II)], were isomers bearing 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, while no anticancer activity was found for both the chloride-free complex (Pt1) and TioxAla. This cytotoxicity, however lower than that of cisplatin, well correlated 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 spectroscopic and spectrometric analysis.
- Published
- 2019