作为抗癌化合物的冠菌素新型1,2,3-三唑衍生物的设计与合成
Design and synthesis of novel 1,2,3-triazole derivatives of coronopilin as anti-cancer compounds.
作者信息
Khazir Jabeena, Hyder Irfan, Gayatri J Laxmi, Prasad Yandrati Leela, Nalla Naresh, Chasoo Gousia, Mahajan Ajay, Saxena A K, Alam M S, Qazi G N, Sampath Kumar Halmuthur M
机构信息
Medicinal Chemistry Division, CSIR - Indian Institute of Integrative Medicine, Jammu 180001, India.
Natural Products Chemistry Division, CSIR - Indian Institute of Chemical Technology, Hyderabad 500007, India.
出版信息
Eur J Med Chem. 2014 Jul 23;82:255-62. doi: 10.1016/j.ejmech.2014.05.053. Epub 2014 May 24.
A series of 1,2,3-triazole coronopilin congeners have been designed and synthesized by employing click chemistry approach starting from parthenin and evaluated for their cytotoxicity against a panel of six human cancer cell lines (PC-3, THP-1, HCT-15, HeLa, A-549 and MCF-7). While many compounds exhibited significant anticancer activity, compound 3a, was found to be the most promising analogue in this series with IC50 values of 3.1 μM on PC-3 cell line. Flow-cytometric studies showed that 1,2,3-triazole derivative-3a induce dose dependent apoptosis in the sub G1 phase. This lead molecule-3a was further studied for NF-κB (p65) transcription factor inhibitory activity using Elisa and western blotting analysis which confirmed concentration dependent inhibitory activity against NF-κB, p65 with 80% inhibition in 24 h at 100 μM.
从小白菊内酯出发，采用点击化学方法设计并合成了一系列1,2,3 - 三唑冠菌素类似物，并评估了它们对六种人类癌细胞系（PC - 3、THP - 1、HCT - 15、HeLa、A - 549和MCF - 7）的细胞毒性。虽然许多化合物表现出显著的抗癌活性，但化合物3a被发现是该系列中最有前景的类似物，在PC - 3细胞系上的IC50值为3.1 μM。流式细胞术研究表明，1,2,3 - 三唑衍生物3a在亚G1期诱导剂量依赖性凋亡。使用酶联免疫吸附测定法（ELISA）和蛋白质印迹分析对先导分子3a的NF - κB（p65）转录因子抑制活性进行了进一步研究，结果证实其对NF - κB p65具有浓度依赖性抑制活性，在100 μM下24小时抑制率达80%。
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