2,3-位四氢-β-咔啉并二酮哌嗪类化合物合成及抗肿瘤活性研究

doi:10.6023/cjoc202603026

摘要/Abstract

利用药物拼合原理合成了30个含不同取代基的四氢-β-咔啉并二酮哌嗪类衍生物。通过MTT法测试了目标化合物对三种肿瘤细胞株(LLC、A-549、NCI-H1666)增殖的抑制活性。结果显示：大多数化合物对这三种肿瘤细胞株表现出了中等至良好的抑制活性,且多数化合物的IC₅₀值低于20 μM。其中,所得的目标化合物对A549细胞系表现出良好的抑制活性,特别是化合物6o和6y对A549细胞表现出优异的抑制活性,且IC₅₀值均低于10 μM。整体来说,化合物6o、6p、6y和化合物6z对LLC、A549和NCI-H1666细胞系表现出良好的抑制活性,且IC₅₀值均低于20 μM,具有潜在的抗肿瘤研究价值。分子对接结果表明,化合物6o和化合物6p与VEGFR-2(PDB:4AGD)的多个氨基酸残基之间存在良好的相互作用。同时,分子动力学模拟结果表明,化合物6p与4AGD之间能保持二者的结合稳定性和构象一致性。

关键词: 四氢-β-咔啉, 二酮哌嗪, 抗肿瘤, 分子对接, 分子动力学模拟

A series of 30 tetrahydro-β-carboline fused diketopiperazine derivatives containing different substituents were synthesized using the principle of drug combination. Their antiproliferative activities were evaluated against three tumor cell lines (LLC, A-549, NCI-H1666) via MTT assay. The results showed that most compounds exhibited moderate to good inhibitory activity against these three tumor cell lines, and the IC₅₀ values of most compounds were below 20 μM. Among them, the target compounds showed good inhibitory activity against A549 cell line, especially compounds 6o and 6p showed excellent inhibitory activity against A549 cell line, with IC₅₀ values below 10 μM. Overall, compounds 6o, 6p, 6y, and 6z exhibit good inhibitory activity against LLC, A549, and NCI-H1666 cell lines, with IC₅₀ values all below 20 μM, indicating potential anti-tumor research value. The molecular docking results indicate that compound 6o and compound 6p have good interactions with multiple amino acid residues of VEGFR-2 (PDB:4AGD). Meanwhile, the molecular dynamics simulation results indicate that the binding stability and conformational consistency between compound 6p and 4AGD can be maintained.

Key words: tetrahydro-β-carboline, diketopiperazine, antitumor, molecular docking, molecular dynamics simulation

引用此文

杨苗, 赵银九, 龚燕川, 张洁, 郭亮. 2,3-位四氢-β-咔啉并二酮哌嗪类化合物合成及抗肿瘤活性研究[J]. 有机化学, doi: 10.6023/cjoc202603026.

Yang Miao, Zhao Yinjiu, Gong Yanchuan, Zhang Jie, Guo Liang. Synthesis and Antitumor Activity Study of 2,3-Substituted Tetrahydro-β-carboline Fused Diketopiperazine Derivatives[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202603026.

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