Arylamidonaphtalene sulfonate compounds as a novel class of heparanase inhibitors

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:27

Article

Rondanin, Riccardo¹  Fochi, Sara¹  Baruchello, Riccardo¹  Bernardi, Tatiana¹  Oliva, Paola¹  Semeraro, Floriana¹  Simoni, Daniele¹  Giannini, Giuseppe² 

[1] Univ Ferrara, Dept Chem & Pharmaceut Sci, Ferrara, Italy

[2] R&D Alfasigma SpA, Med Chem, Via Pontina,Km 30,400, I-00071 Pomezia, RM, Italy

关键词: Antimetastatic activity;    Heparanase inhibitors;    Antitumor agents;   

DOI  :  10.1016/j.bmcl.2017.08.013

来源: Elsevier

【 摘 要 】

The search for antimetastatic agents for cancer therapy may involve the ability of new compounds to maintain the tissue extracellular matrix integrity. Among known factors, heparanase, an endoglucuronidase responsible for heparan sulfate cleavage, is a promising target whose inhibition could represent a strong obstacle for metastatic cancerous mechanisms. The antimetastatic activity of some suramin derivatives reported in literature suggests a possible involvement of the heparanase enzyme. To confirm such hypothesis, we have investigated FCE27266, a molecule known for its antiangiogenic and antimetastatic properties. Other new derivatives were also synthesized and investigated. Our findings revealed that FCE27266 as well as some derivatives have a strong heparanase inhibition activity, together with no cytotoxic power. Moreover, a FCE27266 analogue (SST0546NA1; 17a) resulted also positive to lower gene expression of some proangiogenic factors. (C) 2017 Elsevier Ltd. All rights reserved.

【 授权许可】

Free