细胞毒性
化学
部分
MTT法
蛋白质数据库
三嗪
PI3K/AKT/mTOR通路
立体化学
mTOR抑制剂的发现与发展
对接(动物)
组合化学
体外
激酶
配体(生物化学)
IC50型
结构-活动关系
芳基
生物化学
细胞生长
质子核磁共振
生物活性
1,3,5-三嗪
碳-13核磁共振
受体
细胞凋亡
有机化学
护理部
医学
作者
Sara Ranjbar,Najmeh Edraki,Mahsima Khoshneviszadeh,Alireza Foroumadi,Ramin Miri,Mehdi Khoshneviszadeh
标识
DOI:10.4103/1735-5362.220962
摘要
Mammalian target of rapamycin (mTOR) is a phosphoinositide 3-kinase-related protein kinase which controls cell growth and is frequently deregulated in many cancers. Therefore, mTOR inhibitors are used as antineoplastic agents for cancer treatment. In this study, 1,2,4-triazine derivatives containing different arylidene-hydrazinyl moieties were designed and synthesized. Cytotoxicity of the compounds was evaluated on HL-60 and MCF-7 cell lines by MTT assay. S1, S2 and S3 exhibited good cytotoxic activity on both cell lines with an IC50 range of 6.42 - 20.20 μM. In general, substitution of a five-membered heterocyclic ring containing NO2, such as 5-nitrofuran-2-yl, resulted in the best potency. Molecular docking analysis was performed to study the possible interactions and binding modes of all the triazine derivatives with mTOR receptor. The most promising compound, S1, was well accommodated within the active site and had the least estimated free energy of binding (even less than the inherent ligand of the protein, PDB ID: 4JT6). It is concluded from both MTT assay and docking studies that the arylidene moiety linked to the hydrazinyl part of the structure had a prominent role in cytotoxicity and mTOR inhibitory activity.
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