Synthesis, DNA binding studies, and antiproliferative activity of novel Pt(II)- complexes with an L-alanyl-based ligand(365 views) Riccardi C, Capasso D, Rozza GM, Platella C, Montesarchio D, Di Gaetano S, Marzo T, Pratesi A, Messori L, Roviello GN, Musumeci D
Keywords: Pt(ii)-Complexes, Triazolyl-Thione L-Alanine Ligand, Nmr Spectroscopy, Dna Binding, Cd Spectroscopy, Esi-Ms Spectrometry, Alanine Analogs, Derivatives Metabolism Pharmacology
, Antineoplastic Agents Chemical Synthesis Metabolism Pharmacology
, Cell Line, Tumor
, Coordination Complexes Chemical Synthesis Metabolism Pharmacology
, Dna Genetics Metabolism
, Drug Screening Assays, Antitumor
, G-Quadruplexes
, Humans
, Platinum Chemistry,
Affiliations: *** IBB - CNR ***
Claudia Riccardia§, Domenica Capassob§, Giovanna M. Rozzaa, Chiara Platellaa,
Daniela Montesarchioa, Sonia Di Gaetanoc, Tiziano Marzod,
Alessandro Pratesie, Luigi Messorie, Giovanni N. Rovielloc,*, Domenica Musumecia,c,*
a Department of Chemical Sciences, University of Napoli Federico II, 80126, Napoli, Italy;
b Department of Pharmacy, University of Napoli Federico II, 80131, Napoli, Italy;
c CNR, Institute of Biostructure and Bioimaging, 80134 Napoli, Italy;
d Department of Pharmacy, University of Pisa, 56126, Pisa, Italy;
e Department of Chemistry Ugo Schiff, University of Firenze, 50019 Sesto Fiorentino, Italy.
Domenica Musumeci, Department of Chemical Sciences, University of Napoli Federico II, Via
Cintia, 21, I-80126 Napoli, Italy
E-mail address: domenica.musumeci@unina.it
Phone: +39-081-674143;
E-mail address: giroviel@unina.it
Department of Chemical Sciences, University of Napoli Federico II, 80126 Napoli, Italy.
Department of Pharmacy, University of Napoli Federico II, 80131 Napoli, Italy.
CNR, Institute of Biostructure and Bioimaging, 80134 Napoli, Italy.
References: Not available.
Synthesis, DNA binding studies, and antiproliferative activity of novel Pt(II)- complexes with an L-alanyl-based ligand
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 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, 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 Gquadruplex),
as verified by spectroscopic and spectrometric analysis.
Synthesis, DNA binding studies, and antiproliferative activity of novel Pt(II)- complexes with an L-alanyl-based ligand