Development and Evaluation of 1-Hydroxypyridin-2(1 <i>H</i> )-one Derivatives as Antibacterial Agents against Pathogenic <i>Pseudomonas aeruginosa</i>
The global rise of multidrug-resistant bacteria has prompted an urgent need for new antibiotics, yet resistance continues to outpace discovery due to Gram-negative barriers, drug permeability issues, and limited industry investment. In this study, we synthesized a series of 1-hydroxypyridin-2-(1<i>H</i>)-one derivatives targeting <i>Pseudomonas aeruginosa</i> for analyses of antibacterial efficacy. Among these, <b>LP07</b> displayed potent antibacterial activity across multiple strains, enhanced by subinhibitory colistin. Scanning electron microscopy suggested membrane-associated morphological changes, including surface collapse, shrinkage, and irregular cell shape, consistent with bactericidal effects. Safety profiling showed low CYP inhibition, minimal hERG liability, and no mammalian cytotoxicity. Taken together, <b>LP07</b>'s whole-cell activity and observed membrane effects support its promise as a lead for further optimization.
Authors
- Joo‐Youn Lee (ORCID: https://orcid.org/0000-0001-5685-9875)
- Soo Bong Han (ORCID: https://orcid.org/0000-0002-7831-1832)
- Shujuan Yu (ORCID: https://orcid.org/0000-0002-7958-0057)
- Saemee Song (ORCID: https://orcid.org/0000-0002-3126-2615)
- Seong Soon Kim (ORCID: https://orcid.org/0000-0002-4762-8693)
- Haemi Lee (ORCID: https://orcid.org/0000-0002-7866-4945)
- Soojin Jang (ORCID: https://orcid.org/0000-0002-2921-7196)
- Solomon Girmay
- Hyun Byun (ORCID: https://orcid.org/0000-0003-3296-1992)
- Chang‐Soo Yun (ORCID: https://orcid.org/0000-0002-2814-3797)
- Myung Ae Bae (ORCID: https://orcid.org/0000-0002-2997-5018)
- Hyejin Kim (ORCID: https://orcid.org/0000-0002-6797-2360)
- Hyunjung Lee (ORCID: https://orcid.org/0000-0002-7048-7331)
- Hyung Jun Kim
- Jun Yeon Hwang
- Sandesha Nayak
- Jeehee Suh
Institutions
- University of Science and Technology (YE)
- Institut Pasteur Korea (KR)
- Korea Research Institute of Chemical Technology (KR)
- Sungkyunkwan University (KR)
- Korea University of Science and Technology (KR)
Publication Details
- Journal
- ACS Medicinal Chemistry Letters
- Published
- 2025-12-02
- DOI
- https://doi.org/10.1021/acsmedchemlett.5c00556
- Primary Topic
- Cancer therapeutics and mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00