PDF(Pubmed)
Abstract：
Complex microbial communities have been reported to be involved in endodontic infections. The microorganisms invade the dental pulp leading to pulpitis and initiating pulp inflammation. Fusobacterium nucleatum is a dominant bacterium implicated in both primary and secondary endodontic infections. Drugs targeting the molecular machinery of F. nucleatum will minimize pulp infection. LpxA and LpxD are early acyltransferases involved in the formation of lipid A, a major component of bacterial membranes. The identification of leads which exhibit preference towards successive enzymes in a single pathway can also prevent the development of bacterial resistance. A stringent screening strategy utilizing physicochemical and pharmacokinetic parameters along with a virtual screening approach identified two compounds, Lomefloxacin and Enoxacin, with good binding affinity towards the early acyltransferases LpxA and LpxD. Lomefloxacin and Enoxacin, members of the fluoroquinolone antibiotic class, exhibit wide-ranging activity against diverse bacterial strains. Nevertheless, their effectiveness in the context of endodontic treatment requires further investigation. This study explored the potential of Lomefloxacin and Enoxacin to manage endodontic infections via computational analysis. Moreover, the compounds identified herein serve as a foundation for devising novel combinatorial libraries with enhanced efficacy for endodontic therapeutic strategies.
摘要：
据报道，复杂的微生物群落与牙髓感染有关。微生物侵入牙髓，导致牙髓炎并引发牙髓炎症。核梭杆菌是主要细菌，涉及原发性和继发性牙髓感染。靶向F.核仁的分子机制的药物将最大程度地减少牙髓感染。LpxA和LpxD是参与脂质A形成的早期酰基转移酶，细菌膜的主要组成部分。鉴定在单个途径中对连续酶表现出偏好的前导还可以防止细菌抗性的发展。严格的筛选策略利用物理化学和药代动力学参数以及虚拟筛选方法确定了两种化合物，洛美沙星和依诺沙星，对早期酰基转移酶LpxA和LpxD具有良好的结合亲和力。洛美沙星和依诺沙星，氟喹诺酮类抗生素的成员，对不同的细菌菌株表现出广泛的活性。然而，它们在牙髓治疗中的有效性需要进一步研究.这项研究探索了洛美沙星和依诺沙星通过计算分析管理牙髓感染的潜力。此外，本文鉴定的化合物作为设计新型组合文库的基础,所述组合文库具有增强的用于牙髓治疗策略的功效。
