Synthesis and Antitumor Activity of Novel Terephthalamide Derivatives

doi:10.6023/cjoc202403049

Chinese Journal of Organic Chemistry ›› 2024, Vol. 44 ›› Issue (11): 3497-3504.DOI: 10.6023/cjoc202403049 Previous Articles Next Articles

ARTICLE

新型对苯二甲酰胺衍生物的合成及抗肿瘤活性研究

顾一飞^a^,^b, 吴彩菊^a, 王思琪^a, 张世琳^a, 陆远^a, 司鑫鑫^a^,^*(), 蒋佰玲^c^,^*()

a 江苏海洋大学药学院江苏省海洋药物活性分子筛选重点实验室江苏连云港 222005
b 江苏省海洋资源开发研究院江苏连云港 222005
c 连云港市第二人民医院药学部江苏连云港 222005

收稿日期:2024-03-29 修回日期:2024-04-29 发布日期:2024-05-30
基金资助:
江苏海洋大学人才引进项目(KQ21044); 江苏省双创博士(JSSCBS20221615); 江苏海洋大学大学生实践创新计划(SY202211641640005)

Synthesis and Antitumor Activity of Novel Terephthalamide Derivatives

Yifei Gu^a^,^b, Caiju Wu^a, Siqi Wang^a, Shilin Zhang^a, Yuan Lu^a, Xinxin Si^a,*(), Bailing Jiang^c,*()

a Jiangsu Key Laborratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, Jiangsu 222005
b Jiangsu Institute of Marine Resources Development, Lianyungang, Jiangsu 222005
c Department of Pharmacy, The Second People’s Hospital of Lianyungang, Lianyungang, Jiangsu 222005

Received:2024-03-29 Revised:2024-04-29 Published:2024-05-30
Contact: *E-mail:jiangbailing2018@163.com;sixinxinyd@163.com
Supported by:
Research Project for Talent Introduction of Jiangsu Ocean University(KQ21044); Doctor of Jiangsu Double Innovation(JSSCBS20221615); College Student’s Practice Innovation Program of Jiangsu Ocean University(SY202211641640005)

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Abstract

In order to search for new structural antitumor drugs, a series of terephthalamide derivatives were designed and synthesized, and their antiproliferative activities against human tumor cell lines (PANC-1, MDA-MB-231 and SGC7901) were determined. N¹-(4-Methoxybenzyl)-N⁴-(3-methoxyphenyl)-N¹-(3,4,5-trimethoxyphenyl)terephthalamide (TF) was identified as the most potent compound in antiproliferation against PANC-1 cells with the value of 0.13 μmol/L, which was better than the positive control 5-fluorouracil (16.22 μmol/L). Further mechanistic studies showed that compound TF could inhibit the clonal proliferation in a dose-dependent manner. In addition, compound TF can reduce the adhesive, migrational and invasive of PANC-1cells. These results indicated that compound TF might be developed the antitumor drug.

Key words: terephthalamide, antivity, synthesis

Cite this article

Yifei Gu, Caiju Wu, Siqi Wang, Shilin Zhang, Yuan Lu, Xinxin Si, Bailing Jiang. Synthesis and Antitumor Activity of Novel Terephthalamide Derivatives[J]. Chinese Journal of Organic Chemistry, 2024, 44(11): 3497-3504.

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References 15

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Compd.	R	IC₅₀^a/(µmol/L)
Compd.	R	PANC-1	MDA-MB-231	SGC7901
8a	4-ClC₆H₄CH₂	4.60±0.91	8.14±0.59	0.32±0.08
8b	4-ClC₆H₄	22.21±2.46	53.51±9.10	1.36±0.35
8c	3-ClC₆H₄	24.40±3.46	>100	87.31±13.36
8d	4-CH₃C₆H₄CH₂	2.30±0.42	29.11±6.44	1.95±0.46
8e	4-CH₃C₆H₄	24.24±3.49	9.13±2.22	0.51±0.26
8f	3-CH₃C₆H₄	0.94±0.07	0.72±0.17	0.81±0.34
8g	C₆H₅CH₂	10.29±1.45	30.05±4.7	0.09±0.03
8h	C₆H₅	26.10±0.59	1.44±0.24	0.18±0.04
8i	4-CH₃OC₆H₄	22.27±2.45	30.61±7.50	6.77±1.92
8j (TF)	3-CH₃OC₆H₄	0.13±0.02	39.61±8.00	1.10±0.33
8k	2-CH₃OC₆H₄	25.86±3.43	78.43±5.67	10.64±1.88
8l	4-OHC₆H₄	39.10±2.83	0.08±0.01	1.94±0.58
8m	4-CF₃OC₆H₄	2.22±0.41	2.22±0.26	0.50±0.13
8n	4-CF₃C₆H₄	7.44±0.91	0.38±0.23	0.56±0.21
8o	Morpholineyl	33.19±3.46	20.59±1.89	1.60±0.16
8p	CH₃NHCH₂CH₂N(CH₃)	9.52±2.93	22.49±2.67	7.40±0.62
5-Fu^b		16.22±1.89	13.91±0.33	8.18±1.88

Compd.	R	IC₅₀^a/(µmol/L)
Compd.	R	PANC-1	MDA-MB-231	SGC7901
8a	4-ClC₆H₄CH₂	4.60±0.91	8.14±0.59	0.32±0.08
8b	4-ClC₆H₄	22.21±2.46	53.51±9.10	1.36±0.35
8c	3-ClC₆H₄	24.40±3.46	>100	87.31±13.36
8d	4-CH₃C₆H₄CH₂	2.30±0.42	29.11±6.44	1.95±0.46
8e	4-CH₃C₆H₄	24.24±3.49	9.13±2.22	0.51±0.26
8f	3-CH₃C₆H₄	0.94±0.07	0.72±0.17	0.81±0.34
8g	C₆H₅CH₂	10.29±1.45	30.05±4.7	0.09±0.03
8h	C₆H₅	26.10±0.59	1.44±0.24	0.18±0.04
8i	4-CH₃OC₆H₄	22.27±2.45	30.61±7.50	6.77±1.92
8j (TF)	3-CH₃OC₆H₄	0.13±0.02	39.61±8.00	1.10±0.33
8k	2-CH₃OC₆H₄	25.86±3.43	78.43±5.67	10.64±1.88
8l	4-OHC₆H₄	39.10±2.83	0.08±0.01	1.94±0.58
8m	4-CF₃OC₆H₄	2.22±0.41	2.22±0.26	0.50±0.13
8n	4-CF₃C₆H₄	7.44±0.91	0.38±0.23	0.56±0.21
8o	Morpholineyl	33.19±3.46	20.59±1.89	1.60±0.16
8p	CH₃NHCH₂CH₂N(CH₃)	9.52±2.93	22.49±2.67	7.40±0.62
5-Fu^b		16.22±1.89	13.91±0.33	8.18±1.88

新型对苯二甲酰胺衍生物的合成及抗肿瘤活性研究

Synthesis and Antitumor Activity of Novel Terephthalamide Derivatives

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