Baiseitova Aizhamal, Lee Gihwan, Shah Abdul Bari, Yoon Sanghwa, Kim Jeong Ho, Lee Yong Hyun, Park Ki Hun
Division of Applied Life Science (BK21 plus), IALS, Gyeongsang National University, Jinju 52828, Republic of Korea.
Department of Bio & Medical Big-data (BK4 Program), Gyeongsang National University, 501 Jinju-daero, Jinju 52828, Republic of Korea.
Bioorg Chem. 2022 Oct;127:105978. doi: 10.1016/j.bioorg.2022.105978. Epub 2022 Jun 20.
Artocarpus elasticus is a popular fruit tree in the tropical regions. Primary screenings of methanol extracts of the root bark confirmed its potent inhibition of bacterial neuraminidase (BNA), which plays an essential role in the pathogenesis of many microbial diseases. Assessments of the responsible phytochemicals were conducted by isolating eight compounds (1-8) and two of them (6 and 8) were identified as new compounds. Among the isolates, the dihydrobenzoxanthones attained the highest BNA inhibition with IC values of 0.5 ∼ 3.9 µM. Further investigation of the inhibitory mechanism by Lineweaver-Burk plots revealed the phytochemicals to function as reversible noncompetitive inhibitors. Fluorescence quenching showed their binding affinities were highly correlated with their inhibitory potential dose-dependently. Molecular docking experiments suggested the dihydrobenzoxanthones (4 and 6) as noncompetitive inhibitors of BNA with unique interaction with Tyr435 of BNA in comparison with the mother flavonoid (7).
面包树是热带地区一种常见的果树。对其根皮甲醇提取物的初步筛选证实，它对细菌神经氨酸酶（BNA）有强效抑制作用，而BNA在许多微生物疾病的发病机制中起着至关重要的作用。通过分离出8种化合物（1 - 8）对相关植物化学物质进行了评估，其中两种（6和8）被鉴定为新化合物。在分离出的化合物中，二氢苯并氧杂蒽酮对BNA的抑制作用最强，IC值为0.5至3.9 μM。通过Lineweaver - Burk图对抑制机制的进一步研究表明，这些植物化学物质起可逆非竞争性抑制剂的作用。荧光猝灭表明它们的结合亲和力与它们的抑制潜力呈高度剂量依赖性相关。分子对接实验表明，与母黄酮（7）相比，二氢苯并氧杂蒽酮（4和6）作为BNA的非竞争性抑制剂，与BNA的Tyr435有独特的相互作用。
