Synthesis, antibacterial activity, and biological evaluation of formyl hydroxyamino derivatives as novel potent peptide deformylase inhibitors against drug-resistant bacteria

• 43 formyl hydroxyamino derivatives were rationally designed and synthesized as PDF inhibitors.
• The SAR on P1′, P2′ and P3′ positions of the PDF inhibitors were studied.
• Full set of biological evaluation were carried out to identify PDF inhibitors with good in-vivo efficacy and low toxicity.

Peptide deformylase (PDF) has been identified as a promising target for novel antibacterial agents. In this study, a series of novel formyl hydroxyamino derivatives were designed and synthesized as PDF inhibitors and their antibacterial activities were evaluated. Among the potent PDF inhibitors (1o, 1q, 1o′, 1q′, and 1x), in vivo studies showed that compound 1q possesses mild toxicity, a good pharmacokinetic profile and protective effects. The good in vivo efficacy and low toxicity suggest that this class of compounds has potential for development and use in future antibacterial drugs.

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