Porphyromonas gingivalis is a Gram-negative anaerobic pathogen that can trigger oral dysbiosis as an early event in the pathogenesis of periodontal disease. The FDA-approved drug zafirlukast (ZAF) was recently shown to display antibacterial activity against P. gingivalis. Here, 15 novel ZAF derivatives were synthesized and evaluated for their antibacterial activity against P. gingivalis and for their cytotoxic effects. Most derivatives displayed superior antibacterial activity against P. gingivalis compared to ZAF and its first generation derivatives along with little to no growth inhibition of other oral bacterial species. The most active compounds displayed bactericidal activity against P. gingivalis and less cytotoxicity than ZAF. The superior and selective antibacterial activity of ZAF derivatives against P. gingivalis along with an increased safety profile compared to ZAF suggest these new compounds, especially 14b and 14e, show promise as antibacterials for future studies aimed to test their potential for preventing/treating P. gingivalis-induced periodontal disease.

中文翻译：

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对口腔病原体牙龈卟啉单胞菌具有增强活性的第二代扎鲁司特衍生物

牙龈卟啉单胞菌是一种革兰氏阴性厌氧病原体，可引发口腔生态失调，作为牙周病发病机制的早期事件。FDA 批准的药物扎鲁司特 (ZAF) 最近显示出对牙龈卟啉单胞菌的抗菌活性。在这里，合成了 15 种新型 ZAF 衍生物并评估了它们对牙龈卟啉单胞菌的抗菌活性和细胞毒作用。与 ZAF 及其第一代衍生物相比，大多数衍生物对牙龈卟啉单胞菌表现出优异的抗菌活性，并且对其他口腔细菌种类几乎没有或没有生长抑制作用。最具活性的化合物显示出对牙龈卟啉单胞菌的杀菌活性且细胞毒性比 ZAF 小。ZAF 衍生物对牙龈卟啉单胞菌的卓越和选择性抗菌活性以及与 ZAF 相比增加的安全性表明，这些新化合物，尤其是14b和14e，显示出作为未来研究的抗菌剂的希望，旨在测试它们预防/治疗牙龈卟啉单胞菌的潜力。牙龈引起的牙周病。