N-(α-桐酸酰基)三唑类化合物的制备及其生物活性

doi:10.3969/j.issn.0253-2417.2022.03.004

林产化学与工业 ›› 2022, Vol. 42 ›› Issue (3): 27-33.doi: 10.3969/j.issn.0253-2417.2022.03.004

N-(α-桐酸酰基)三唑类化合物的制备及其生物活性

成江¹^,², 谢普军¹^,², 黄立新¹^,²^,*(), 张彩虹¹^,², 刘璐婕¹^,²

1. 中国林业科学研究院林产化学工业研究所；生物质化学利用国家工程实验室；国家林业和草原局林产化学工程重点实验室；江苏省生物质能源与材料重点实验室，江苏南京 210042
2. 南京林业大学江苏省林业资源高效加工利用协同创新中心，江苏南京 210037

收稿日期:2021-03-03 出版日期:2022-06-28 发布日期:2022-07-04
通讯作者: 黄立新 E-mail:l_x_huang@163.com
作者简介:黄立新，研究员，博士生导师，研究领域为天然资源化学利用；E-mail: l_x_huang@163.com
成江(1992—)，男, 湖南永州人，博士生，从事桐油化学利用研究
基金资助:
江苏省自然科学基金资助项目(BK20181124);国家重点研发计划资助项目(2017YFD0601001)

Synthesis and Biological Activity of N-(α-Eleostearic Acyl) Triazole Derivatives

Jiang CHENG¹^,², Pujun XIE¹^,², Lixin HUANG¹^,²^,*(), Caihong ZHANG¹^,², Lujie LIU¹^,²

1. Institute of Chemical Industry of Forest Products, CAF; National Engineering Lab. for Biomass Chemical Utilization; Key Lab. of Chemical Engineering of Forest Products, National Forestry and Grassland Administration; Key Lab. of Biomass Energy and Material, Jiangsu Province, Nanjing 210042, China
2. Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Nanjing Forestry University, Nanjing 210037, China

Received:2021-03-03 Online:2022-06-28 Published:2022-07-04
Contact: Lixin HUANG E-mail:l_x_huang@163.com

摘要/Abstract

摘要：

以α-桐酸为原料，制备得到一系列N-(α-桐酸酰基)三唑类化合物：N-(α-桐酸酰基)-3, 5-二溴-1, 2, 4-三唑(3a)、N-(α-桐酸酰基)-1, 2, 4-三唑(3b)、N-(α-桐酸酰基)-3-巯基-1, 2, 4-三唑(3c)、N-(α-桐酸酰基)-5-硝基-1, 2, 4-三唑(3d)、N-(α-桐酸酰基)-1, 2, 3苯骈三唑(3e)、3-α-桐酸酰基-1, 2, 4-三唑(3f)、4-α-桐酸酰基-1, 2, 4-三唑(3g)，并用FT-IR、¹H NMR、¹³C NMR和MS对产物进行了确证。生物活性实验结果表明：化合物3a和3e对肝癌细胞Hep G2、直肠癌细胞DLD-1和乳腺癌细胞MCF-7均有抑制效果，化合物3d对乳腺癌细胞MCF-7的半数抑制浓度(IC₅₀，25.12 μmol/L)优于阳性对照5-氟尿嘧啶(5-Fu)的抗肿瘤效果。所有目标化合物对白色念珠菌均具有较好的抑制活性，但对大肠杆菌和金黄色葡萄球菌的抑制效果不显著。化合物3e对白色念珠菌的IC₅₀达到22.69 mg/L，与阳性对照5-氟胞嘧啶的抗菌效果相近，具有作为药物开发的潜力。

关键词: α-桐酸, 三唑, 生物活性, 衍生物

Abstract:

A series of N-(α-eleostearic acyl) triazole compounds derived from α-eleostearic acid were synthesized: N-(α-eleostearic acyl)-3, 5-dibromo-1, 2, 4-triazole(3a), N-(α-eleostearic acyl)-1, 2, 4-triazole(3b), N-(α-eleostearic acyl)-3-sulfhydryl-1, 2, 4-triazole(3c), N-(α-eleostearic acyl)-5-nitro-1, 2, 4-triazole(3d), N-(α-eleostearic acyl)-1, 2, 3-benzotriazole(3e), 3-(α-eleostearic acyl)-1, 2, 4-triazole(3f), 4-(α-eleostearic acyl)-1, 2, 4-triazole(3g). The products were confirmed by FT-IR, ¹H NMR, ¹³C NMR and MS. The results of biological activity experiments showed that compound 3a and 3e had inhibitory effect on hepatocarcinoma cells Hep G2, rectal carcinoma cells DLD-1 and breast cancer cells MCF-7. The 50% inhibition concentration(IC₅₀) of compound 3d on MCF-7 was 25.12 μmol/L, which was better than the IC₅₀ of 5-fluorouracil(5-Fu). All compounds had good inhibitory activity against Candida albicans, and inhibitory activities on against Escherichia coli and Staphylococcus aureus were not significant. The IC₅₀ of compound 3e against Candida albicans was 22.96 mg/L, which was similar to 5-flucytosine and indicated that it had the potential of drug development.

Key words: α-eleostearic acid, triazole, biological activity, derivatives

中图分类号:

TQ35

成江, 谢普军, 黄立新, 张彩虹, 刘璐婕. N-(α-桐酸酰基)三唑类化合物的制备及其生物活性[J]. 林产化学与工业, 2022, 42(3): 27-33.

Jiang CHENG, Pujun XIE, Lixin HUANG, Caihong ZHANG, Lujie LIU. Synthesis and Biological Activity of N-(α-Eleostearic Acyl) Triazole Derivatives[J]. Chemistry and Industry of Forest Products, 2022, 42(3): 27-33.

图/表 4

图1

表1

表2

表3

参考文献 16

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化合物 compound	抑制率inhibition rates(20 μmol/L)/%			抑制率inhibition rates(200 μmol/L)/%
化合物 compound	人肝癌Hep G2	人直肠癌DLD-1	人乳腺癌MCF-7	人肝癌Hep G2	人直肠癌DLD-1	人乳腺癌MCF-7
3a	8.64	7.57	5.99	82.53	91.07	86.69
3b	0.23	0.82	0.07	1.54	7.01	2.89
3c	1.77	0.96	3.33	2.93	8.74	7.35
3d	4.33	5.31	35.06	5.72	14.88	92.83
3e	6.08	7.31	6.49	85.85	93.88	92.18
3f	1.98	3.38	1.47	9.83	3.45	4.05
3g	1.97	2.17	1.45	6.36	3.89	3.37
5-Fu	10.67	25.75	13.16	94.43	96.38	92.76

化合物 compound	IC₅₀/(μmol·L^-1)
化合物 compound	人肝癌细胞 Hep G2	人直肠癌细胞 DLD-1	人乳腺癌细胞 MCF-7
3a	112.76	101.22	97.99
3d	＞200	＞200	25.12
3e	115.00	104.39	107.89
5-Fu	42.23	29.89	40.70

化合物 compounds	IC₅₀/(mg·L^-1)
化合物 compounds	大肠杆菌E. coli	白色念珠菌C. albicans	金黄色葡萄球菌S. aureus
3a	＞500	120.21	＞500
3b	＞500	111.5	＞500
3c	＞500	49.16	＞500
3d	＞500	53.94	＞500
3e	148.20	22.69	457.83
3f	＞500	108.01	＞500
3g	＞500	384.20	＞500
氨苄青霉素钠ampicillin sodium	57.51	—	3.71
5-氟胞嘧啶5-fluorocytosine	—	19.35	—

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N-(α-桐酸酰基)三唑类化合物的制备及其生物活性

Synthesis and Biological Activity of N-(α-Eleostearic Acyl) Triazole Derivatives

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