Department of Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Bioorg Med Chem Lett. 2011 Aug 1;21(15):4528-32. doi: 10.1016/j.bmcl.2011.05.129. Epub 2011 Jun 12.
Selective inhibitors of human peptide deformylase (HsPDF) are predicted to constitute a new class of antitumor agents. We report the identification of benzofuran-4,5-diones as the first known selective HsPDF inhibitors and we describe their selectivity profile in a panel of metalloproteases. We characterize their structure-activity relationships for antitumor activity in a panel of cancer cell lines, and we assess their in vivo efficacy in a mouse xenograft model. Our results demonstrate that selective HsPDF inhibitors based on the benzofuran-4,5-dione scaffold constitute a novel class of antitumor agents that are potent in vitro and in vivo.
选择性人肽脱甲酰酶（HsPDF）抑制剂有望成为一类新型抗肿瘤药物。我们报告了苯并呋喃-4,5-二酮作为首个已知的选择性 HsPDF 抑制剂的发现，并描述了它们在一系列金属蛋白酶中的选择性特征。我们研究了它们在一系列癌细胞系中的抗肿瘤活性的构效关系，并评估了它们在小鼠异种移植模型中的体内疗效。我们的结果表明，基于苯并呋喃-4,5-二酮骨架的选择性 HsPDF 抑制剂构成了一类新型的抗肿瘤药物，在体外和体内均具有很强的活性。
