Sanni David Morakinyo, Fatoki Toluwase Hezekiah, Kolawole Ayodele Oluseyi, Akinmoladun Afolabi Clement
Enzyme Biotechnology and Bioinformatics Unit, Department of Biochemistry, Federal University of Technology, PMB 704 Akure, Nigeria.
Biochemical Pharmacology and Toxicology Unit, Department of Biochemistry, Federal University of Technology, PMB 704 Akure, Nigeria.
In Silico Pharmacol. 2017 Sep 2;5:8. doi: 10.1007/s40203-017-0028-y. eCollection 2017.
(Noni) fruit has a long history of dietary use in tropical regions of the world. Pharmacological properties that have been attributed to the fruit include anti-inflammatory, anti-cancer, and antioxidant properties. Xeronine, a small alkaloid which has been patented (US4543212) is one of the bioactive compounds of Noni fruit, which is believed to be capable of modifying the molecular structure of specific inactive proteins thereby regulating proper folding to active enzymes. Despite reports of the potential of Xeronine as therapeutic agent, its presence is controversial and its structure has not been explored. In this study, standard chemoinformatics tools and servers such as and have been employed to predict its possible structure. In addition, synthetic xeronine structures based on the known bioactive components of Noni fruit were designed. Results showed that the hypothetical structure of xeronine provided by the patent inventor is a mystery based on its <5% probable protein targets and no similarity match to the US Food and Drug Administration (FDA) approved drugs and experimental compounds by in silico evaluation. By constrast, final designed xeronine structure possess all the features that were described in the patent document, and has >40% probable protein targets related to neurodegenerative diseases such as Alzheimer's disease (AD), which possibly justifies the key function stated in the patent.
诺丽果在世界热带地区作为食物使用已有很长历史。诺丽果具有的药理特性包括抗炎、抗癌和抗氧化特性。赛诺宁是一种已获专利（美国专利号4543212）的小生物碱，是诺丽果的生物活性化合物之一，据信它能够改变特定无活性蛋白质的分子结构，从而调节其正确折叠成活性酶。尽管有报道称赛诺宁有作为治疗剂的潜力，但其存在存在争议，其结构也尚未被研究。在本研究中，已使用诸如……等标准化学信息学工具和服务器来预测其可能的结构。此外，基于诺丽果已知生物活性成分设计了合成赛诺宁结构。结果表明，专利发明者提供的赛诺宁假设结构基于其小于5%的可能蛋白质靶点，且通过计算机模拟评估与美国食品药品监督管理局（FDA）批准的药物和实验化合物无相似匹配，是个谜。相比之下，最终设计的赛诺宁结构具备专利文件中描述的所有特征，并且有超过40%的可能蛋白质靶点与诸如阿尔茨海默病（AD）等神经退行性疾病相关，这可能证明了专利中所述的关键功能。
