Novel zafirlukast derivatives exhibit selective antibacterial activity against Porphyromonas gingivalis† †Electronic supplementary information (ESI) available: Details of all experimental procedures for (i) the synthesis and characterization of all compounds and intermediates generated in this study, (ii) the effect of zafirlukast derivatives on bacterial viability, (iii) the bactericidal effect of zafirlukast derivatives, and (iv) the cytotoxic effect of zafirlukast derivatives on oral epitheli

• Published in: MedChemComm Vol. 10; no. 6; pp. 926 - 933
• Main Authors: Thamban Chandrika, Nishad, Fosso, Marina Y., Alimova, Yelena, May, Abigail, Gonzalez, Octavio A., Garneau-Tsodikova, Sylvie
• Format: Journal Article
• Language: English
• Published: Royal Society of Chemistry 10.06.2019
• Subjects: Chemistry
• ISSN: 2040-2503; 2040-2511
• DOI: 10.1039/c9md00074g

Eleven new zafirlukast derivatives selective and bactericidal against Porphyromonas gingivalis . Periodontal disease is an oral chronic immune-inflammatory disease highly prevalent worldwide that is initiated by specific oral bacterial species leading to local and systemic effects. The development of new preventive/therapeutic strategies to specifically target oral periodontopathogens without perturbing oral microbiome species normally colonizing the oral cavity is needed. The fast and affordable strategy of repositioning of already FDA-approved drugs can be an answer to the development of novel treatments against periodontal pathogens such as Porphyromonas gingivalis . Herein, we report the synthesis and antibacterial activity of novel zafirlukast derivatives, their bactericidal effect, and their cytotoxicity against oral epithelial cell lines. Many of these derivatives exhibited superior antibacterial activity against P. gingivalis compared to the parent drug zafirlukast. The most promising compounds were found to be selective against P. gingivalis and they were bactericidal in their activity. Finally, we demonstrated that these potent derivatives of zafirlukast provided a better safety profile against oral epithelial cells compared to zafirlukast.