Hydrazyl hydroxycoumarins as new potential conquerors towards Pseudomonas aeruginosa

Bioorg Med Chem Lett. 2024 Mar 15;103:129709. doi: 10.1016/j.bmcl.2024.129709. Online ahead of print.ABSTRACTA class of unique hydrazyl hydroxycoumarins (HHs) as novel structural scaffold was developed to combat dreadful bacterial infections. Some HHs could effectively suppress bacterial growth at low concentrations, especially, pyridyl HH 7 exhibited a good inhibition against Pseudomonas aeruginosa 27853 with a low MIC value of 0.5 μg/mL, which was 8-fold more active than norfloxacin. Furthermore, pyridyl HH 7 with low hemolytic activity and low cytotoxicity towards NCM460 cells showed much lower trend to induce the drug-resistant development than norfloxacin. Preliminarily mechanism exploration indicated that pyridyl HH 7 could eradicate the integrity of bacterial membrane, result in the leakage of intracellular proteins, and interact with bacterial DNA gyrase via non-covalent binding, and ADME analysis manifested that compound 7 gave good pharmacokinetic properties. These results suggested that the newly developed hydrazyl hydroxycoumarins as potential multitargeting antibacterial agents should be worthy of further investigation for combating bacterial infection.PMID:38494040 | DOI:10.1016/j.bmcl.2024.129709
Source: Bioorganic and Medicinal Chemistry Letters - Category: Chemistry Authors: Source Type: research
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