Selective Inhibition of the Periodontal Pathogen Porphyromonas gingivalis by Third-Generation Zafirlukast Derivatives.

Periodontal diseases are inflammatory diseases triggered by pathogenic oral bacterial species, such as Porphyromonas gingivalis . Zafirlukast (ZAF) has displayed antibacterial activity against P. gingivalis . Herein, we report the design, synthesis, and selective antibacterial activity of 14 novel third-generation ZAF derivatives. Two second-generation ZAF derivatives were tested as they were not previously tested against P. gingivalis ATCC 33277. Most third-generation derivatives displayed superior/selective antibacterial activity against P. gingivalis compared to ZAF and its second-generation derivatives. The compounds displayed bactericidal activity against P. gingivalis , inhibited biofilm growth, displayed no hemolytic activity, and displayed less cytotoxicity against mammalian cells than ZAF. The superior/selective antibacterial activity of ZAF derivatives against P. gingivalis , increased safety profile, and inhibition of biofilm growth compared to ZAF indicate that the compounds, especially 21a , 21b , and 24g , show promise as antibacterial agents for future studies to test their potential for preventing and treating P. gingivalis -induced periodontal diseases.