三种毛蕨属药用植物中CDC25磷酸酯酶抑制剂的定向发现研究

CDC25磷酸酯酶在细胞有丝分裂过程中发挥重要调控作用，是一类与肿瘤密切相关的关键蛋白。申请人前期研究发现毛蕨属植物中含有结构新颖的查尔酮-香豆素杂合类化合物，该类成分对CDC25磷酸酯酶具有显著抑制活性,并对多种肿瘤细胞具有生长抑制作用。本项目以三种毛蕨属药用植物华南毛蕨、干旱毛蕨和齿牙毛蕨为研究对象，通过整合亲和超滤质谱与代谢组学的研究方法，以亲和超滤为活性筛选平台，以代谢组学方法挖掘具有CDC25酶抑制活性的潜力化合物，建立一种基于活性的代谢组研究方法，以期定向发现高活性的天然CDC25酶抑制剂，并评价其抗肿瘤药理活性。本项目旨在从毛蕨属药用植物中快速、定向发现新颖的具有CDC25酶抑制活性的抗肿瘤化合物，同时建立一种基于活性的代谢组学技术从植物中发现具有酶抑制活性化合物的研究方法。

CDC25 phosphatases play an important role in regulation procedure of cell mitosis and are key proteins closely related to tumor. In previous study the applicant found that plants of Cyclosorus sp. were rich in novel chalcone-coumarin hybrids, which were inhibitors of CDC25 phosphatases and potential anti-tumor agents. In present project, an activity-based metabolomics workflow, established by integrating methods of affinity ultrafiltration mass spectrometry and metabolomics, is introduced into study on targeted discovery of natural CDC25 inhibitors from three Cyclosorus sp. medicinal plants, including C. parasiticus, C. aridus and C. dentatus. The main research contents include: Affinity ultrafiltration screening on Cyclosorus sp. plant extracts and CDC25 phosphatases; Metabolomic analysis for identification of bioactive compounds; Tracking isolation of bioactive compounds from plant extracts; And CDC25 phosphatases inhibition assay and anticancer research of the compounds. This project aims at discovery of novel anti-cancer compounds from Cyclosorus sp. medicinal plants and, moreover, establishing a reliable workflow for discovery of bioactive compounds by activity-based metabolomics.