Novel pyrazole-5-carboxamide and pyrazole-pyrimidine derivatives: synthesis and anticancer activity.
Novel pyrazole-5-carboxamide and pyrazole-pyrimidine derivatives: synthesis and anticancer activity.
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DOI：
10.1016/j.ejmech.2014.12.013
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发表时间：
2015-01
影响因子：
6.7
通讯作者：
J. Shi;Wenjian Tang;X. Qi;Rong Li;X. Liu
中科院分区：
文献类型：
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作者：
J. Shi;Wenjian Tang;X. Qi;Rong Li;X. Liu
设计合成了一系列新型的吡唑-5-甲酰胺和吡唑嘧啶类化合物。所有化合物均在体外对MGC-803、SGC-7901和BCap-37细胞株具有抗增殖活性。结果表明，化合物8a，8and8对MGC-803细胞具有较强的抑制活性。流式细胞仪分析结果表明，化合物8能抑制MGC-803细胞的增殖。化合物8对端粒酶的抑制活性最强，IC50值为1.02±0.08μM。对化合物8E进行了对接模拟，得到了可能的结合模型，其中赖氨酸189、赖氨酸372、赖氨酸249和天冬氨酸254可能是影响端粒酶活性的关键残基。
A series of novel pyrazole-5-carboxamide and pyrazole–pyrimidine derivatives were designed and synthesized. All compounds have been screened for their antiproliferative activity against MGC-803, SGC-7901 and Bcap-37 cell linesin vitro. The results revealed that compounds8a,8cand8eexhibited strong inhibitory activity against MGC-803 cell line. The flow cytometric analysis result showed that compound8ecould inhibit MGC-803 proliferation. Some title compounds were tested against telomerase, and compound8eshowed the most potent inhibitory activity with IC50value at 1.02 ± 0.08 μM. The docking simulation of compound8ewas performed to get the probable binding model, among them, LYS 189, LYS 372, LYS 249 and ASP 254 may be the key residues for the telomerase activity.