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Updated: Jul 18, 2026

Production and Testing of Antimicrobial Peptides and Their Mimics
Published on: April 10, 2026
Further exploration of antimicrobial ketodihydronicotinic acid derivatives by multiple parallel syntheses
Jane B Laursen1, John Nielsen, Torsten Haack
1Department of Medicinal Chemistry, Chemical Methodology and Library Development Center of Excellence, Kansas University, 1251 Wescoe Hall Drive, Lawrence, KS 66045, USA.
Abstract:
A synthetic reexamination of a series of ketodihydronicotinic acid class antibacterial agents was undertaken in an attempt to improve their therapeutic potential. A convenient new synthesis was developed involving hetero Diels-Alder chemistry producing 74 new analogs in a multiple parallel synthetic manner and these were examined in vitro for their antimicrobial potential. Several compounds demonstrated significant broad-spectrum activity against clinically derived bacterial strains but previously known 1-(2,4-difluorophenyl)-6-(4-dimethylaminophenyl)-4-pyridone-3-carboxylic acid (7) remained the most potent compound in this class. Cross-resistance with ciprofloxacin supported a commonality of mode of action. Permiabilization of Escherichia coli cells by polymyxin B significantly enhanced potency with these agents suggesting that poor cellular uptake was primarily responsible for the disappointing activity against bacteria that some of the analogs exhibited.
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