Aruwa Christiana Eleojo, Sabiu Saheed
Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology, Durban, KwaZulu-Natal, South Africa.
Chem Biodivers. 2025 Sep;22(9):e202403220. doi: 10.1002/cbdv.202403220. Epub 2025 Apr 28.
South African plants are an underutilized metabolite source for novel antimicrobials targeting key quorum sensing (QS) systems like the Staphylococcus aureus AgrA. AgrA-modulating metabolites constitute a new approach to reducing resistance development. This study created a library of 1211 metabolites from 266 South African plants with antimicrobial action. Metabolites' anti-QS activities were assessed using advanced computational methods. Molecular docking showed top five metabolites (hinokiflavone, asphodelin, elliptinone, mamegakinone, and robustaflavone). Most leads conformed to the Lipinski's rule of 5. Dynamics simulation revealed closest ∆G for robustaflavone (-25.50 kcal/mol) and hinokiflavone (-20.94 kcal/mol) compared to the standard (-26.59 kcal/mol). Leads interacted with key residues (Asn62/201, Asp75/214, Arg94/233, and Asn95/234) and a high number of interactions that ensured thermodynamic stability and compactness. The identified leads could be key mechanistic contributors to the antimicrobial activity of their inherent plants. Both the plants and metabolites (robustaflavone and hinokiflavone) could be further explored following structural modification as QS inhibitors.
南非植物是一种未得到充分利用的代谢物来源，可用于开发针对关键群体感应（QS）系统（如金黄色葡萄球菌AgrA）的新型抗菌剂。调节AgrA的代谢物是减少耐药性产生的一种新方法。本研究创建了一个来自266种具有抗菌作用的南非植物的1211种代谢物的文库。使用先进的计算方法评估了代谢物的抗QS活性。分子对接显示了排名前五的代谢物（扁柏黄酮、阿福豆苷、椭圆玫瑰树碱、豆香醌和粗壮黄酮）。大多数先导化合物符合Lipinski的五规则。动力学模拟显示，与标准值（-26.59 kcal/mol）相比，粗壮黄酮（-25.50 kcal/mol）和扁柏黄酮（-20.94 kcal/mol）的最接近∆G。先导化合物与关键残基（Asn62/201、Asp75/214、Arg94/233和Asn95/234）相互作用，并存在大量确保热力学稳定性和紧凑性的相互作用。所鉴定的先导化合物可能是其固有植物抗菌活性的关键机制贡献者。植物和代谢物（粗壮黄酮和扁柏黄酮）在结构修饰后作为QS抑制剂都可进一步探索。
