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. PortaPrimo
;G. FacchettiSecondo
;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.File | Dimensione | Formato | |
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