De Luna Joseph G, Gonzales Shanahi Chelledie B, Nuqui Jimuel Jan M, Capinding Evalyn S, Sacdalan Corazon D
Department of Chemistry, Technological University of the Philippines Ayala Boulevard, Ermita Manila Philippines.
RSC Adv. 2024 Aug 14;14(35):25579-25585. doi: 10.1039/d4ra04709e. eCollection 2024 Aug 12.
Thrombotic disorders pose a global health threat, emphasizing the urgent need for effective management strategies. This study explores the potential of bioactive compounds derived from guava leaves in inhibiting coagulation factor IXa (CFIXa) using methods. Using GC-MS, bioactive compounds extracted from guava leaf through ethanol maceration were identified. Pharmacokinetic properties were elucidated using SwissADME. Molecular docking with AutoDock Vina was used to investigate the interactions with CFIXa. CFIXa was modeled with pysimm/LAMMPS and analyzed with CastP for active site identification. The setup with a higher solvent concentration and lower surface area yielded the highest percent yield (78.541 g, 39.27%). Among the 28 identified bioactive compounds, predominantly terpenoids, only seven exhibited suitable pharmacokinetic properties for oral ingestion and drug development. Docking analysis revealed favorable binding of these compounds to CFIXa (-7.6:-5.3). This study shows inhibition of coagulation factor IXa, thus bridging the ambiguity surrounding the effect of guava leaves on hemostasis. These findings also reveal that guava leaf extract harbors bioactive compounds with potential as coagulation pathway inhibitors, promising novel avenues for thrombotic disorder management.
血栓形成性疾病对全球健康构成威胁，凸显了对有效管理策略的迫切需求。本研究采用多种方法探索番石榴叶衍生的生物活性化合物在抑制凝血因子IXa（CFIXa）方面的潜力。使用气相色谱 - 质谱联用（GC-MS）鉴定了通过乙醇浸渍从番石榴叶中提取的生物活性化合物。利用瑞士药物设计软件（SwissADME）阐明了其药代动力学性质。使用自动对接软件（AutoDock Vina）进行分子对接，以研究与CFIXa的相互作用。用pysimm/LAMMPS对CFIXa进行建模，并使用CastP分析其活性位点。溶剂浓度较高且表面积较小的设置产生了最高的产率百分比（78.541克，39.27%）。在鉴定出的28种生物活性化合物中，主要为萜类化合物，只有7种表现出适合口服摄入和药物开发的药代动力学性质。对接分析表明这些化合物与CFIXa具有良好的结合（-7.6:-5.3）。本研究表明凝血因子IXa受到抑制，从而消除了围绕番石榴叶对止血作用的模糊性。这些发现还揭示了番石榴叶提取物含有具有作为凝血途径抑制剂潜力的生物活性化合物，为血栓形成性疾病的管理开辟了新的途径。
