Department of Restorative Dental Sciences, College of Dentistry, Jazan University, Jazan 45142, Saudi Arabia.
Specialized Dental Canter, Ministry of Health, Jazan 45142, Saudi Arabia.
Int J Mol Sci. 2024 Jul 15;25(14):7727. doi: 10.3390/ijms25147727.
Endodontic infections pose significant challenges in dental practice due to their persistence and potential complications. Among the causative agents, stands out for its ability to form biofilms and develop resistance to conventional antibiotics, leading to treatment failures and recurrent infections. The urgent need for alternative treatments arises from the growing concern over antibiotic resistance and the limitations of current therapeutic options in combating -associated endodontic infections. Plant-based natural compounds offer a promising avenue for exploration, given their diverse bioactive properties and potential as sources of novel antimicrobial agents. In this study, molecular docking and dynamics simulations are employed to explore the interactions between SrtA, a key enzyme in , and plant-based natural compounds. Analysis of phytocompounds through molecular docking unveiled several candidates with binding energies surpassing that of the control drug, ampicillin, with pinocembrin emerging as the lead compound due to its strong interactions with key residues of SrtA. Comparative analysis with ampicillin underscored varying degrees of structural similarity among the study compounds. Molecular dynamics simulations provided deeper insights into the dynamic behavior and stability of protein-ligand complexes, with pinocembrin demonstrating minimal conformational changes and effective stabilization of the N-terminal region. Free energy landscape analysis supported pinocembrin's stabilizing effects, further corroborated by hydrogen bond analysis. Additionally, physicochemical properties analysis highlighted the drug-likeness of pinocembrin and glabridin. Overall, this study elucidates the potential anti-bacterial properties of selected phytocompounds against infections, with pinocembrin emerging as a promising lead compound for further drug development efforts, offering new avenues for combating bacterial infections and advancing therapeutic interventions in endodontic practice.
牙髓感染在牙科实践中构成了重大挑战，因为它们具有持续性和潜在的并发症。在病原体中， 因其能够形成生物膜并对常规抗生素产生耐药性而引人注目，这导致了治疗失败和反复感染。对抗生素耐药性的日益关注以及当前治疗方案在对抗 相关牙髓感染方面的局限性，促使人们迫切需要替代治疗方法。植物源性天然化合物因其多样的生物活性特性和作为新型抗菌剂来源的潜力，为探索提供了一个有前途的途径。在这项研究中，采用分子对接和动力学模拟来研究 SrtA（ 中的关键酶）与植物源性天然化合物之间的相互作用。通过分子对接分析植物化合物，发现了几种与对照药物氨苄西林相比具有结合能超过氨苄西林的候选化合物，其中松属素因与 SrtA 的关键残基具有强烈的相互作用而成为主导化合物。与氨苄西林的比较分析突出了研究化合物之间在结构上存在不同程度的相似性。分子动力学模拟提供了对蛋白质-配体复合物动态行为和稳定性的更深入了解，松属素表现出最小的构象变化和对 N 端区域的有效稳定作用。自由能景观分析支持了松属素的稳定作用，氢键分析进一步证实了这一点。此外，物理化学性质分析突出了松属素和甘草素的类药性。总的来说，这项研究阐明了选定植物化合物对 感染的潜在抗菌特性，松属素作为进一步药物开发的有前途的先导化合物脱颖而出，为对抗细菌感染和推进牙髓病治疗干预提供了新的途径。
