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Coumarins from Magydaris pastinacea as inhibitors of the tumour-associated carbonic anhydrases IX and XII: isolation, biological studies and in silico evaluation.
Journal of Enzyme inhibition and Medicinal Chemistry ( IF 5.6 ) Pub Date : 2020-01-17 , DOI: 10.1080/14756366.2020.1713114
Benedetta Fois 1 , Simona Distinto 1 , Rita Meleddu 1 , Serenella Deplano 1 , Elias Maccioni 1 , Costantino Floris 2 , Antonella Rosa 3 , Mariella Nieddu 3 , Pierluigi Caboni 1 , Claudia Sissi 4 , Andrea Angeli 5 , Claudiu T Supuran 5 , Filippo Cottiglia 1
Affiliation  

In an in vitro screening for human carbonic anhydrase (hCA) inhibiting agents from higher plants, the petroleum ether and ethyl acetate extracts of Magydaris pastinacea seeds selectively inhibited hCA IX and hCA XII isoforms. The phytochemical investigation of the extracts led to the isolation of ten linear furocoumarins (1-10), four simple coumarins (12-15) and a new angular dihydrofurocoumarin (11). The structures of the isolated compounds were elucidated based on 1 D and 2 D NMR, MS, and ECD data analysis. All isolated compounds were inactive towards the ubiquitous cytosolic isoform hCA I and II (Ki > 10,000 nM) while they were significantly active against the tumour-associated isoforms hCA IX and XII. Umbelliprenin was the most potent coumarin inhibiting hCA XII isoform with a Ki of 5.7 nM. The cytotoxicity of the most interesting compounds on HeLa cancer cells was also investigated.

中文翻译:

来自Magydaris pastinacea的香豆素作为与肿瘤相关的碳酸酐酶IX和XII的抑制剂:分离,生物学研究和计算机评估。

在对高等植物中人碳酸酐酶(hCA)抑制剂的体外筛选中,Magydaris pastinacea种子的石油醚和乙酸乙酯提取物选择性抑制hCA IX和hCA XII亚型。对提取物的植物化学研究导致分离出十个线性呋喃香豆素(1-10),四个简单的香豆素(12-15)和新的角二氢呋喃香豆素(11)。基于1 D和2 D NMR,MS和ECD数据分析,阐明了分离出的化合物的结构。所有分离的化合物均对普遍存在的胞质亚型hCA I和II无活性(Ki> 10,000 nM),而对与肿瘤相关的亚型hCA IX和XII具有显着活性。伞形肾上腺素是最有效的香豆素抑制hCA XII亚型,Ki为5.7 nM。
更新日期:2020-04-20
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