| Literature DB >> 28324784 |
Federica Porta1, Giorgio Facchetti1, Nicola Ferri2, Arianna Gelain3, Fiorella Meneghetti1, Stefania Villa1, Daniela Barlocco1, Daniela Masciocchi1, Akira Asai4, Nao Miyoshi4, Silvia Marchianò5, Byoung-Mog Kwon6, Yena Jin6, Valentina Gandin7, Cristina Marzano7, Isabella Rimoldi8.
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·HCl showed cytotoxic effects on HCT-116 cells (IC50 = 95.2 μM) and a selective ability to interact with STAT3 (IC50 = 8.2 μM) versus STAT1 (IC50 > 30 μM). Its corresponding platinum complex Pt-3 exhibited an increased cytotoxicity (IC50 = 18.4 μM) and a stronger interaction with STAT3 (IC50 = 1.4 μM), 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.Entities:
Keywords: Antitumor agents; Cytotoxic activity; DNA-interaction; Platinum diamine complex; Protein–protein interactions
Mesh：
Substances：
Year: 2017 PMID： 28324784 DOI： 10.1016/j.ejmech.2017.03.017
Source DB: PubMed Journal: Eur J Med Chem ISSN： 0223-5234 Impact factor: 6.514