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

Authors :: Porta F
Facchetti G
Ferri N
Gelain A
Meneghetti F
Villa S
Barlocco D
Masciocchi D
Asai A
Miyoshi N
Marchianò S
Kwon BM
Jin Y
Gandin V
Marzano C
Rimoldi I
Source :: European journal of medicinal chemistry [Eur J Med Chem] 2017 May 05; Vol. 131, pp. 196-206. Date of Electronic Publication: 2017 Mar 15.
Publication Year :: 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·HCl showed cytotoxic effects on HCT-116 cells (IC <subscript>50</subscript>  = 95.2 μM) and a selective ability to interact with STAT3 (IC <subscript>50</subscript>  = 8.2 μM) versus STAT1 (IC <subscript>50</subscript>  > 30 μM). Its corresponding platinum complex Pt-3 exhibited an increased cytotoxicity (IC <subscript>50</subscript>  = 18.4 μM) and a stronger interaction with STAT3 (IC <subscript>50</subscript>  = 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.<br /> (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Subjects :: Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Cell Proliferation drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Molecular Structure
Organoplatinum Compounds chemical synthesis
Organoplatinum Compounds chemistry
Oxadiazoles chemistry
Platinum chemistry
Structure-Activity Relationship
Tumor Cells, Cultured
Antineoplastic Agents pharmacology
Organoplatinum Compounds pharmacology
Oxadiazoles pharmacology
Platinum pharmacology
STAT3 Transcription Factor antagonists & inhibitors

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