Rozano Lina, Abdullah Zawawi Muhammad Redha, Ahmad Muhamad Aizuddin, Jaganath Indu Bala
Agri-Omics and Bioinformatics Programme, Biotechnology and Nanotechnology Research Centre, Malaysian Agricultural Research and Development Institute, 43400 Selangor, Malaysia.
Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, 43600 Bangi, Malaysia.
Adv Bioinformatics. 2017;2017:5124165. doi: 10.1155/2017/5124165. Epub 2017 Aug 8.
The inhibition of dipeptidyl peptidase-IV (DPPIV) is a popular route for the treatment of type-2 diabetes. Commercially available gliptin-based drugs such as sitagliptin, anagliptin, linagliptin, saxagliptin, and alogliptin were specifically developed as DPPIV inhibitors for diabetic patients. The use of in treating diabetes had been reported in various in vitro experiments. However, an understanding of the inhibitory actions of bioactive compounds on DPPIV is still lacking and this may provide crucial information for the development of more potent and natural sources of DPPIV inhibitors. Evaluation of bioactive compounds for potent DPPIV inhibitors was computationally conducted using Lead IT and iGEMDOCK software, and the best free-binding energy scores for bioactive compounds were evaluated in comparison with the commercial DPPIV inhibitors, sitagliptin, anagliptin, linagliptin, saxagliptin, and alogliptin. Drug-likeness and absorption, distribution, metabolism, and excretion (ADME) analysis were also performed. Based on molecular docking analysis, four of the identified bioactive compounds in , 3-caffeoylquinic acid, 5-O-caffeoylquinic acid, 3,4-dicaffeoylquinic acid, and -5--coumaroylquinic acid, resulted in lower free-binding energy scores when compared with two of the commercially available gliptin inhibitors. The results revealed that bioactive compounds in are potential natural inhibitors of DPPIV.
抑制二肽基肽酶-IV（DPPIV）是治疗2型糖尿病的常用途径。市售的基于格列汀的药物，如西他列汀、阿格列汀、利格列汀、沙格列汀和阿洛格列汀，是专门为糖尿病患者开发的DPPIV抑制剂。在各种体外实验中已报道了其在治疗糖尿病方面的应用。然而，对生物活性化合物对DPPIV的抑制作用仍缺乏了解，这可能为开发更有效和天然来源的DPPIV抑制剂提供关键信息。使用Lead IT和iGEMDOCK软件对生物活性化合物作为强效DPPIV抑制剂进行了计算评估，并将生物活性化合物的最佳自由结合能得分与市售DPPIV抑制剂西他列汀、阿格列汀、利格列汀、沙格列汀和阿洛格列汀进行了比较。还进行了类药性和吸收、分布、代谢及排泄（ADME）分析。基于分子对接分析，所鉴定的生物活性化合物中的四种，即3-咖啡酰奎尼酸、5-O-咖啡酰奎尼酸、3,4-二咖啡酰奎尼酸和-5--香豆酰奎尼酸，与两种市售格列汀抑制剂相比，产生了更低的自由结合能得分。结果表明，该生物活性化合物是DPPIV的潜在天然抑制剂。
