新型均三嗪化合物的合成及抗肿瘤活性

doi:10.6023/cjoc202408021

摘要/Abstract

利用活性拼接原理, 设计了新型均三嗪化合物. 以三聚氯氰、胺和查尔酮为起始原料, 合成了一系列新型均三嗪化合物, 其结构通过¹H NMR、¹³C NMR、FT-IR、高分辨率质谱(HRMS)和高效液相色谱(HPLC)进行了表征. 采用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐(MTT)法评价所得化合物对人肺癌细胞(A549)、人宫颈癌细胞(HeLa)、人乳腺癌细胞(MCF-7)和人结肠癌细胞(SW620)的体外抗增殖活性. 结果表明, 所得化合物均具有良好的抗肿瘤作用. 其中(E)-1-(4-((4,6-二甲基吗啉基-1,3,5-三嗪-2-基)氧基)苯基)-3-(噻吩-2-基)丙-2-烯-1-酮(3bg)对A549、HeLa和MCF-7细胞系均表现出显著的抑制活性, 具有广谱性. (E)-1-(4-((4,6-二甲基吗啉基-1,3,5-三嗪-2-基)氧基)苯基)-3-苯基丙-2-烯-1-酮(3bb)对人乳腺癌细胞(MCF-7)具有最强的体外抗肿瘤活性, IC₅₀为16.4 μmol/L, 是该实验中活性最高的化合物.

关键词: 均三嗪化合物, α,β-不饱和酮, 抗肿瘤活性

Employing the principle of active moiety concatenation, a novel series of symmetrical triazine compounds were designed. A series of novel triazine compounds were synthesized using cyanuric chloride, amines, and chalcones as the initial reactants. The structures of these compounds were characterized through FT-IR, ¹H-NMR, ¹³C-NMR, high-resolution mass spectrometry (HRMS) and high performance liquid chromatography (HPLC). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetra- zolium bromide (MTT) assay was employed to evaluate the in vitro anti-proliferative activity of the new s-triazine compounds against human lung cancer cells (A549), human cervical cancer cells (HeLa), human breast cancer cells (MCF-7) and human colon cancer cells (SW620). The findings indicated that several compounds exhibited promising antitumor effects. Notably, (E)-1-(4-((4,6-dimorpholino-1,3,5-triazin-2-yl)oxy)phenyl)-3-(thiophen-2-yl)prop-2-en-1-one (3bg) demonstrated efficacy as a broad-spectrum anticancer agent, exhibiting significant activity against the A549, HeLa, and MCF-7 cell lines. Furthermore, (E)-1-(4-((4,6-dimorpholino-1,3,5-triazin-2-yl)oxy)phenyl)-3-phenylprop-2-en-1-one (3bb) displayed the most potent in vitro antitumor activity against the MCF-7 cell line with an IC₅₀ value of 16.4 μmol/L, establishing it as the most active compound in assay.

Key words: s-triazine compounds, α,β-unsaturated ketones, antitumor activity

引用此文

贺甜甜, 孙立娇, 吕佳慧, 李进京, 杜永红. 新型均三嗪化合物的合成及抗肿瘤活性[J]. 有机化学, 2025, 45(7): 2577-2585.

Tiantian He, Lijiao Sun, Jiahui Lü, Jinjing Li, Yonghong Du. Synthesis and Antitumor Activity of Innovative Homotriazine Compounds[J]. Chinese Journal of Organic Chemistry, 2025, 45(7): 2577-2585.

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Compound	IC₅₀/(μmol•L^－1)
Compound	A549	Hela	MCF-7	SW620
Cisplatin	8.9±0.42	6.2±1.12	14.3±2.22	18.6±1.35
3aa	35.4±0.51	120.3±1.39	81.8±1.79	26.8±6.92
3ab	20.8±0.52	15.6±1.39	30.5±4.38	94.5±0.50
3ac	41.3±0.77	92.6±0.64	75.1±2.40	42.7±2.11
3ad	100.8±1.54	71.4±4.00	60.5±2.35	69.9±2.77
3ae	18.5±0.58	26.3±1.14	33.7±7.84	41.4±2.80
3af	88.6±1.84	51.2±6.22	66.8±1.74	36.6±0.76
3bb	28.6±1.34	42.2±0.45	16.4±3.22	45.5±1.12
3bc	39.4±5.05	45.9±1.22	25.7±2.27	40.6±0.45
3bd	68.6±0.59	72.3±2.15	46.5±0.57	77.8±0.90
3be	12.8±5.60	16.9±1.05	35.6±4.27	40.8±0.79
3bf	26.8±1.57	69.3±0.95	70.5±1.84	47.7±0.92
3bg	19.6±0.44	18.2±12.63	19.6±2.98	53.3±18.74
3ca	90.6±36.70	77.3±0.88	72.6±3.00	81.1±9.16
3cb	46.6±0.31	56.6±0.10	61.7±2.78	43.8±4.82
3cc	91.6±3.93	75.5±10.18	42.6±0.22	83.6±2.45
3cd	69.6±7.01	77.4±11.34	92.5±23.97	81.3±7.72
3ce	41.5±0.52	56.8±1.09	67.6±4.87	48.3±4.53
3cf	88.2±35.98	94.3±4.93	105.3±46.64	115.4±22.42

Compound	IC₅₀/(μmol•L^－1)
Compound	A549	Hela	MCF-7	SW620
Cisplatin	8.9±0.42	6.2±1.12	14.3±2.22	18.6±1.35
3aa	35.4±0.51	120.3±1.39	81.8±1.79	26.8±6.92
3ab	20.8±0.52	15.6±1.39	30.5±4.38	94.5±0.50
3ac	41.3±0.77	92.6±0.64	75.1±2.40	42.7±2.11
3ad	100.8±1.54	71.4±4.00	60.5±2.35	69.9±2.77
3ae	18.5±0.58	26.3±1.14	33.7±7.84	41.4±2.80
3af	88.6±1.84	51.2±6.22	66.8±1.74	36.6±0.76
3bb	28.6±1.34	42.2±0.45	16.4±3.22	45.5±1.12
3bc	39.4±5.05	45.9±1.22	25.7±2.27	40.6±0.45
3bd	68.6±0.59	72.3±2.15	46.5±0.57	77.8±0.90
3be	12.8±5.60	16.9±1.05	35.6±4.27	40.8±0.79
3bf	26.8±1.57	69.3±0.95	70.5±1.84	47.7±0.92
3bg	19.6±0.44	18.2±12.63	19.6±2.98	53.3±18.74
3ca	90.6±36.70	77.3±0.88	72.6±3.00	81.1±9.16
3cb	46.6±0.31	56.6±0.10	61.7±2.78	43.8±4.82
3cc	91.6±3.93	75.5±10.18	42.6±0.22	83.6±2.45
3cd	69.6±7.01	77.4±11.34	92.5±23.97	81.3±7.72
3ce	41.5±0.52	56.8±1.09	67.6±4.87	48.3±4.53
3cf	88.2±35.98	94.3±4.93	105.3±46.64	115.4±22.42