New Pt(II) complexes (Pt-1-3) bearing 1,2,5-oxadiazole ligands (1-3) were synthesized, characterized and evaluated for their ability to disrupt STAT3 dimerization. Ligand 3 center dot HC1 showed cytotoxic effects on HCT-116 cells (IC50 = 95.2 mu M) and a selective ability to interact with STAT3 (IC50 = 8.2 mu M) versus STATI (IC50 > 30 mu M). Its corresponding platinum complex Pt -3 exhibited an increased cytotoxicity (IC50 = 18.4 mu M) and a stronger interaction with STAT3 (IC50 = 1.4 mu M), leading to inhibition of its signaling pathway. Pt -3 was also evaluated in cell-based assays for its action on p53 expression and on STAT3 phosphorylation. In syngeneic murine Lewis lung carcinoma (LLC) implanted in C57BL/6 mice, Pt 3 showed a higher antitumor activity with fewer side effects than cisplatin.

An in vivo active 1,2,5-oxadiazole Pt(II) complex : a promising anticancer agent endowed with STAT3 inhibitory properties / F. Porta, G. Facchetti, N. Ferri, A. Gelain, F. Meneghetti, S. Villa, D. Barlocco, D. Masciocchi, A. Asai, N. Miyoshi, S. Marchianò, B. Kwon, Y. Jin, V. Gandin, C. Marzano, I. Rimoldi. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 131(2017 May 05), pp. 196-206. [10.1016/j.ejmech.2017.03.017]

An in vivo active 1,2,5-oxadiazole Pt(II) complex : a promising anticancer agent endowed with STAT3 inhibitory properties

F. Porta
Primo
;
G. Facchetti
Secondo
;
A. Gelain
;
F. Meneghetti;S. Villa;D. Barlocco;D. Masciocchi;S. Marchianò;I. Rimoldi
Ultimo
2017

Abstract

New Pt(II) complexes (Pt-1-3) bearing 1,2,5-oxadiazole ligands (1-3) were synthesized, characterized and evaluated for their ability to disrupt STAT3 dimerization. Ligand 3 center dot HC1 showed cytotoxic effects on HCT-116 cells (IC50 = 95.2 mu M) and a selective ability to interact with STAT3 (IC50 = 8.2 mu M) versus STATI (IC50 > 30 mu M). Its corresponding platinum complex Pt -3 exhibited an increased cytotoxicity (IC50 = 18.4 mu M) and a stronger interaction with STAT3 (IC50 = 1.4 mu M), leading to inhibition of its signaling pathway. Pt -3 was also evaluated in cell-based assays for its action on p53 expression and on STAT3 phosphorylation. In syngeneic murine Lewis lung carcinoma (LLC) implanted in C57BL/6 mice, Pt 3 showed a higher antitumor activity with fewer side effects than cisplatin.
DNA-interaction; Cytotoxic activity; Platinum diamine complex; Antitumor agents; Protein-protein interactions
Settore CHIM/03 - Chimica Generale e Inorganica
Settore CHIM/08 - Chimica Farmaceutica
Settore BIO/14 - Farmacologia
   SISTEMI NATURALI E SINTETICI AD ATTIVITA' ANTITUMORALE
   MINISTERO DELL'ISTRUZIONE E DEL MERITO
   20105YY2HL_007
5-mag-2017
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/491251
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