Identification of benzofuran-4,5-diones as novel and selective non-hydroxamic acid, non-peptidomimetic based inhibitors of human peptide deformylase

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.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► We identified benzofuran-4,5-diones as selective human peptide deformylase inhibitors. ► We describe their selectivity profile in a panel of metalloproteases. ► We characterize their structure–activity relationships in a panel of cancer cell lines. ► We assess their in vivo efficacy in a mouse xenograft model. ► Benzofuran-4,5-diones constitute a novel class of antitumor agents.