Rondanin Riccardo, Fochi Sara, Baruchello Riccardo, Bernardi Tatiana, Oliva Paola, Semeraro Floriana, Simoni Daniele, Giannini Giuseppe
Department of Chemical and Pharmaceutical Sciences, University of Ferrara, Italy.
Department of Chemical and Pharmaceutical Sciences, University of Ferrara, Italy.
Bioorg Med Chem Lett. 2017 Sep 15;27(18):4421-4425. doi: 10.1016/j.bmcl.2017.08.013. Epub 2017 Aug 8.
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.
寻找用于癌症治疗的抗转移药物可能涉及新化合物维持组织细胞外基质完整性的能力。在已知因素中，乙酰肝素酶是一种负责切割硫酸乙酰肝素的内切葡糖醛酸酶，是一个有前景的靶点，其抑制作用可能对转移性癌机制构成强大障碍。文献报道的一些苏拉明衍生物的抗转移活性表明乙酰肝素酶可能参与其中。为了证实这一假设，我们研究了FCE27266，一种以其抗血管生成和抗转移特性而闻名的分子。还合成并研究了其他新衍生物。我们的研究结果表明，FCE27266以及一些衍生物具有很强的乙酰肝素酶抑制活性，且无细胞毒性。此外，一种FCE27266类似物（SST0546NA1；17a）对降低一些促血管生成因子的基因表达也呈阳性。
