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

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.