Synthesis and preliminary antibacterial evaluation of hydroxamic acid and N-formyl hydroxylamine derivatives bearing oxazole ring

Zhang, Datong; Huo, Lingyan; Lü, Lei; Yu, Qiong; Wang, Jianwu; Yang, Yanyan

doi:10.1007/s00044-012-0141-8

Cited by 2 publications

(2 citation statements)

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“…[16] Therefore, new strategies were explored by the replacement of hydrolyzable peptidic structures with different non-peptidic scaffolds such as heterocyclic azoles which serve as amide bioisosteres. [17] Structural characterization or co-crystal studies of PDF inhibitors suggested that hydroxamic acid forms a strong complex with various transition metals and the mechanism of inhibition involves its binding to the metal ion along with amino acid residues present in the active site of the enzyme. [18] In PDF, iron is present as Fe 2 + ion and the oxidation state of iron plays an important role in the regulation of enzyme activity.…”

Section: Introductionmentioning

confidence: 99%

“…Although these PDF inhibitors exhibited broad‐spectrum antibacterial activity but showed poor pharmacokinetic properties, weak in vivo activity due to their deceptive peptidic characteristics . Therefore, new strategies were explored by the replacement of hydrolyzable peptidic structures with different non‐peptidic scaffolds such as heterocyclic azoles which serve as amide bioisosteres …”

Section: Introductionmentioning

confidence: 99%

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Ferulic Hydroxamic Acid Triazole Hybrids as Peptide Deformylase Inhibitors: Synthesis, Molecular Modelling and Biological Evaluation

et al. 2020

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Design and development of peptide deformylase (PDF) inhibitors has gained attention as it is a highly conserved and specific enzyme for bacterial protein synthesis. This makes it a specific and attractive drug target. Therefore, based on the targeted drug-discovery approach, a series of ferulic acid-based nonpeptidic hydroxamic acid-triazole hybrids was synthesized. All the semi-synthetic compounds (8 a-p) were evaluated against a panel of Gram-positive and Gram-negative bacterial strains. Most of the compounds showed antibacterial activities against S. pneumoniae while few were active against E. coli. Among all, the compound 8 j showed strong potency against S. pneumoniae with IC 50 value 34.57 μg/mL whereas for E. coli the observed IC 50 was 66.20 μg/mL. Growth kinetics study showed the bacteriostatic nature of compound 8 j against S. pneumoniae. Interestingly, in the studied concentration range, no significant hemolysis or cytotoxicity was observed towards human cells, suggesting the non-toxic nature of compound 8 j. Molecular docking studies showed that compound 8 j occupies the same active site where actinonin (a known inhibitor of PDF) binds and it also mimics the mode of interactions by offering significant interactions with the corresponding amino acid residues of PDF. The outcome of this study suggested the potential implications of the present scaffold for the development of antibacterial molecules targeting PDF.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%