Li Xingjian, Payne Daniel T, Ampolu Badarinath, Bland Nicholas, Brown Jane T, Dutton Mark J, Fitton Catherine A, Gulliver Abigail, Hale Lee, Hamza Daniel, Jones Geraint, Lane Rebecca, Leach Andrew G, Male Louise, Merisor Elena G, Morton Michael J, Quy Alex S, Roberts Ruth, Scarll Rosanna, Schulz-Utermoehl Timothy, Stankovic Tatjana, Stevenson Brett, Fossey John S, Agathanggelou Angelo
School of Chemistry, University of Birmingham, Edgbaston, Birmingham, West Midlands B15 2TT, UK. Email:
Sygnature Discovery, The Discovery Building, BioCity, Pennyfoot Street, Nottingham, NG1 1GR, UK.
Medchemcomm. 2019 Aug 1;10(8):1379-1390. doi: 10.1039/c9md00297a.
Parthenolide is a natural product that exhibits anti-leukaemic activity, however, its clinical use is limited by its poor bioavailability. It may be extracted from and protocols for growing, extracting and derivatising it are reported A novel parthenolide derivative with good bioavailability and pharmacological properties was identified through a screening cascade based on anti-leukaemic activity and calculated "drug-likeness" properties, and pharmacokinetics studies and hERG liability testing. studies showed the most promising derivative to have comparable anti-leukaemic activity to DMAPT, a previously described parthenolide derivative. The newly identified compound was shown to have pro-oxidant activity and molecular docking studies indicate a prodrug mode of action. A synthesis scheme is presented for the production of amine used in the generation of .
小白菊内酯是一种具有抗白血病活性的天然产物，然而，其临床应用因生物利用度差而受到限制。它可以从[具体来源未提及]中提取，并且有关于其种植、提取和衍生化的方案报道。通过基于抗白血病活性、计算的“类药”性质、药代动力学研究和人醚-à-去极化相关基因（hERG）安全性测试的筛选级联，鉴定出一种具有良好生物利用度和药理特性的新型小白菊内酯衍生物。[具体研究未提及]研究表明，最有前景的衍生物具有与先前描述的小白菊内酯衍生物DMAPT相当的抗白血病活性。新鉴定的化合物显示具有促氧化活性，分子对接研究表明其作用方式为前药。本文给出了用于生成[具体产物未提及]的胺的合成方案。
