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.

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► 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.