2. Academic Validation
  3. Development and Evaluation of 1‑Hydroxypyridin-2(1 H)‑one Derivatives as Antibacterial Agents against Pathogenic Pseudomonas aeruginosa

Development and Evaluation of 1‑Hydroxypyridin-2(1 H)‑one Derivatives as Antibacterial Agents against Pathogenic Pseudomonas aeruginosa

  • ACS Med Chem Lett. 2025 Dec 2;16(12):2477-2485. doi: 10.1021/acsmedchemlett.5c00556.
Sandesha Nayak 1 2,  Berehe Solomon Girmay 1 2,  Ha Jeong Byun 1,  Seong Soon Kim 1,  Sunjong Yu 1,  Jun Yeon Hwang 1,  Hyung Jun Kim 3,  Hyunjung Lee 3,  Joo-Youn Lee 1 2,  Haemi Lee 1,  Myung Ae Bae 1,  Chang-Soo Yun 1,  Soojin Jang 3,  Jeehee Suh 1,  Saemee Song 1,  Soo Bong Han 1 2 4,  Hyejin Kim 1 2 4
Affiliations

Affiliations

  • 1 Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea.
  • 2 Department of Medicinal Chemistry and Pharmacology, University of Science and Technology, Daejeon 34113, Republic of Korea.
  • 3 Antibacterial Resistance Laboratory, Institut Pasteur Korea, Seongam-si, Gyeonggi-do 13488, Republic of Korea.
  • 4 School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
PMID: 41403992 DOI: 10.1021/acsmedchemlett.5c00556
Abstract

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-(1H)-one derivatives targeting Pseudomonas aeruginosa for analyses of Antibacterial efficacy. Among these, LP07 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, LP07's whole-cell activity and observed membrane effects support its promise as a lead for further optimization.

Keywords

1-hydroxypyridin-2(1H)-one derivatives; LpxC inhibition; MDR pathogens; MIC; Pseudomonas aeruginosa; antibacterial agents.

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