| 引用本文: | 陈佩文,陈嘉烨,陈志红,龚先玲.MELK小分子抑制剂的虚拟筛选及体外活性研究[J].中国现代应用药学,2025,42(4):21-30. |
| Chen Peiwen,Chen Jiaye,Chen Zhihong,Gong.Virtual Screening of and in vitro Study on Small-molecule MELK InhibitorsCHEN Peiwen1, CHEN Jiaye, CHEN Zhihong, GONG Xianling* (School of pharmacy, Guangdong Medical University, Dongguan Guangdong 523808)[J].Chin J Mod Appl Pharm(中国现代应用药学),2025,42(4):21-30. |
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| 摘要: |
| 目的 研究以MELK为靶标,通过虚拟筛选和体外活性实验,从中药博落回中筛选抑制结直肠癌的小分子抑制剂。方法 通过文献检索博落回中的苯并菲啶类生物碱成分,确定为小分子化合物(配体),运用 AutoDock Vina 软件将这些化合物与MELK对接,根据打分值虚拟筛选出博落回中潜在抑制MELK激酶的化学成分。采用MTT法研究化合物对结直肠癌细胞的增殖抑制作用,Western blot法检测细胞PARP、Caspase-3和MELK蛋白的表达。结果 分子对接显示44个化合物均能与MELK蛋白形成稳定对接,22个化合物具有较强的结合能力。体外实验结果显示ETS、DHS、ADS三种化合物均能呈浓度和时间依赖性的抑制结直肠癌细胞的增殖,下调MELK蛋白的表达,且ETS下调CRC细胞PARP、Caspase-3蛋白表达,上调Cleaved PARP和Cleaved Caspase-3蛋白表达。结论 综合虚拟筛选和体外实验,筛选出3个抑制MELK蛋白的苯并菲啶类化合物,为研发新型的MELK小分子抑制剂治疗结直肠癌提供实验依据。 |
| 关键词: 分子对接 博落回 结直肠癌 MELK抑制剂 |
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| 基金项目:广东省中医药局项目(NO. 20201182)； 广东医科大学博士启动项目(NO. B2019029)；广东医科大学强校基金(NO. 4SG23006G) |
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| Virtual Screening of and in vitro Study on Small-molecule MELK InhibitorsCHEN Peiwen1, CHEN Jiaye, CHEN Zhihong, GONG Xianling* (School of pharmacy, Guangdong Medical University, Dongguan Guangdong 523808) |
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Chen Peiwen, Chen Jiaye, Chen Zhihong, Gong
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School of pharmacy, Guangdong Medical University
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| Abstract: |
| OBJECTIVE MELK was used as a target to screen small molecule inhibitors on colorectal cancer from Macleaya cordata, a traditional Chinese medicine. METHODS The benzophenanthridine alkaloids from Macleaya cordata were collected through consulting literature materials and identified as a small molecule compound (ligand). They were docked with MELK by AutoDock Vina software. The potential chemical components that inhibited MELK kinase were screened according to the score. The effect of the compounds on colorectal cancer cells was detected by MTT assay. The expression of apoptosis-related and MELK proteins was analyzed by Western blot. RESULTS Molecular docking results showed that 44 compounds could be stable docking with MELK protein, and 22 compounds have a relatively strong ability to bind with MELK protein. The experimental results demonstrated that ETS, DHS and ADS could inhibit the proliferation of CRC cells in a concentration- and time-dependent manner, down-regulate the protein expression MELK respectively. CONCLUSIONS By virtual screening and in vitro experiments, three benzophenanthridine compounds that inhibited MELK protein were screened, providing an experimental basis for the development of new small molecule MELK inhibitors for the treatment of colorectal cancer. |
| Key words: molecular docking Macleaya cordata colorectal cancer MELK inhibitor |
