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光辉菌素的抗增殖潜力:抗癌药物开发的先导物

Antiproliferative Potential of Gloriosine: A Lead for Anticancer Drug Development.

作者信息

Goel Bharat, Dey Biswajit, Chatterjee Essha, Tripathi Nancy, Bhardwaj Nivedita, Kumar Sanjay, Guru Santosh Kumar, Jain Shreyans K

机构信息

Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, Uttar Pradesh, India.

Department of Biological Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, Telangana, India.

出版信息

ACS Omega. 2022 Aug 12;7(33):28994-29001. doi: 10.1021/acsomega.2c02688. eCollection 2022 Aug 23.

Abstract

Gloriosine, a colchicine-like natural product, is widely obtained from roots. Despite having remarkable anticancer potential, colchicine could not pave its way to the clinic, while gloriosine is yet to be investigated for its pharmacological effects. In the present work, 14 compounds, including gloriosine, were isolated from the roots and were characterized by NMR spectroscopy. Gloriosine () was evaluated for its antiproliferative activity against a panel of 15 human cancer cell lines of different tissues and normal breast cells. Gloroisine () displayed significant antiproliferative activity against various cancer cell lines selectively, with IC values ranging from 32.61 to 100.28 nM. Further, gloriosine () was investigated for its apoptosis-inducing ability and found to form apoptotic bodies. It also inhibited A549 cell migration in the wound healing assay. Finally, molecular docking studies were performed to explore the possible binding modes of gloriosine with the colchicine-binding site of tubulin protein. Our findings suggested that gloriosine might be a potential lead for anticancer drug discovery.

摘要

格洛里辛是一种类似秋水仙碱的天然产物,广泛存在于根部。尽管秋水仙碱具有显著的抗癌潜力,但它未能进入临床应用,而格洛里辛的药理作用尚未得到研究。在本研究中,从根部分离出了包括格洛里辛在内的14种化合物,并通过核磁共振光谱对其进行了表征。对格洛里辛()针对15种不同组织的人类癌细胞系和正常乳腺细胞的抗增殖活性进行了评估。格洛罗辛()对各种癌细胞系具有显著的选择性抗增殖活性,IC值范围为32.61至100.28 nM。此外,对格洛里辛()的诱导凋亡能力进行了研究,发现其能形成凋亡小体。在伤口愈合实验中,它还抑制了A549细胞的迁移。最后,进行了分子对接研究,以探索格洛里辛与微管蛋白的秋水仙碱结合位点的可能结合模式。我们的研究结果表明,格洛里辛可能是抗癌药物发现的潜在先导化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2146/9404168/fff5cae2ca11/ao2c02688_0002.jpg

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