Oxadiazole Pt(II) complexes: promising STAT3 inhibitors in cancer therapy

STAT3 (Signal Transducer and Activator of Transcription 3) is a latent cytosolic protein overexpressed in various cancer cell lines which was found to participate in oncogenesis by stimulating cell proliferation and preventing apoptosis and whose inhibition has been recently validated as target for cisplatin-resistant malignancies [1,2]. Furthermore, previous studies have shown that blocking constitutively activated STAT3 signaling leads to tumor cell apoptosis, with minimal effect on normal cells. Starting from MD77compound, that we previously reported for its ability to disrupt STAT3 dimerization [3], AC33 derivative was selected for further investigations, due to its higher selectivity over STAT1 and Grb2, as evidenced by the AlphaScreen-based assay. Taking into account the positive biological results recorded for Pt-based inhibitors in cisplatin-resistant ovarian cancer, AC33 was employed as ligand for the synthesis of the corresponding Pt(II) complex, which resulted endowed with both STAT3 inhibitory properties and the ability to disrupt DNA integrity in HCT116 cancer cell line.