Design, Synthesis and in vitro Anti-Cancer Activity of Novel Ethyl 4-Oxo-2-iminothiazolidin-5-ylidene Acetates

doi:10.6023/cjoc202210023

Chinese Journal of Organic Chemistry ›› 2023, Vol. 43 ›› Issue (4): 1452-1461.DOI: 10.6023/cjoc202210023 Previous Articles Next Articles

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4-氧代-2-亚胺基噻唑烷-5-亚基乙酸乙酯类化合物的设计、合成及抗癌活性

钟玉梅, 邹小颖, 卓小丫, 王逸涵, 申佳奕, 郑绿茵^*(), 郭维^*()

赣南师范大学有机药物化学重点实验室江西赣州 341000

收稿日期:2022-10-21 修回日期:2022-11-23 发布日期:2022-12-14
通讯作者: 郑绿茵, 郭维
基金资助:
国家自然科学基金(22167002); 国家自然科学基金(21867001); 江西省教育厅(GJJ201429); 赣南师范大学研究生创新(YCX21A027)

Design, Synthesis and in vitro Anti-Cancer Activity of Novel Ethyl 4-Oxo-2-iminothiazolidin-5-ylidene Acetates

Yumei Zhong, Xiaoying Zou, Xiaoya Zhuo, Yihan Wang, Jiayi Shen, Lüyin Zheng(), Wei Guo()

Key Laboratory of Organo-pharmaceutical Chemistry of Jiangxi Province, Gannan Normal University,Ganzhou, Jiangxi 341000

Received:2022-10-21 Revised:2022-11-23 Published:2022-12-14
Contact: Lüyin Zheng, Wei Guo
Supported by:
National Natural Science Foundation of China(22167002); National Natural Science Foundation of China(21867001); Education Department of Jiangxi Province(GJJ201429); Graduate Innovation Research Project of Gannan Normal University(YCX21A027)

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Abstract

A series of novel ethyl 4-oxo-2-iminothiazolidin-5-ylidene acetate derivatives were synthesized through the three- component coupling annulation of amines, isothiocyanates and diethyl but-2-ynedioates. The obtained compounds were assayed in vitro for their anti-cancer activities against human liver cancer (HepG2) and human breast cancer (MCF-7) cell lines by standard methyl thiazolyl tetrazolium (MTT) method, most of which exhibited significant cytotoxicity. In particular, ethyl (Z)-2-((Z)-2-((3,4-dichlorophenyl)imino)-3-(3-(4-methylpiperazin-1-yl)propyl)-4-oxothiazolidin-5-ylidene)-acetate (4r) displayed the highest level of cytotoxicity compared with cisplatin, and its IC₅₀ values for HepG2 and MCF-7 cells were 0.88 and 0.80 μmol/L, respectively. Their preliminary structure-activity relationship was also discussed. The remarkable cytotoxic nature of these substances against cancer cells could be considered as promising chemotherapeutic agents to be developed in future.

Key words: ethyl 4-oxo-2-iminothiazolidin-5-ylidene acetate, anti-cancer activity, structure-based drug design, structure- activity relationship

Cite this article

Yumei Zhong, Xiaoying Zou, Xiaoya Zhuo, Yihan Wang, Jiayi Shen, Lüyin Zheng, Wei Guo. Design, Synthesis and in vitro Anti-Cancer Activity of Novel Ethyl 4-Oxo-2-iminothiazolidin-5-ylidene Acetates[J]. Chinese Journal of Organic Chemistry, 2023, 43(4): 1452-1461.

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Fig. & Tab. 5

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Compd.	IC_50/(μmol•L^－1)		Lipophilicity factor (ChemOffice)
Compd.	HepG2	MCF-7	log P	Clog P
4a	10.97±3.14	11.05±1.06	2.02	2.21
4b	1.47±0.21	1.56±0.09	2.58	2.93
4c	5.53±0.38	6.05±0.40	2.85	3.08
4d	1.20±0.17	1.74±0.33	2.94	3.10
4e	1.82±0.15	1.27±0.02	2.58	2.93
4f	3.14±0.38	3.15±0.23	2.85	3.08
4g	4.78±1.08	6.05±0.40	2.92	3.24
4h	6.84±0.84	5.91±0.41	1.89	2.13
4i	5.12±0.87	9.96±0.87	2.18	2.36
4j	3.10±0.51	3.71±0.25	2.58	2.93
4k	2.37±0.04	3.30±0.27	2.85	3.08
4l	2.33±0.31	1.23±0.15	2.94	3.10
4m	2.13±0.28	1.06±0.08	0.76	1.96
4n	47.20±2.37	42.18±3.27	1.76	2.22
4o	1.03±0.15	2.48±0.24	2.33	2.50
4p	1.99±0.21	3.65±0.29	3.13	3.64
4q	18.46±1.68	3.40±0.82	2.33	2.50
4r	0.88±0.12	0.80±0.11	3.13	3.64
4s	2.28±0.68	1.20±0.06	3.86	3.98
4t	13.29±2.43	7.32±0.78	3.48	3.71
4u	>50	26.64±4.72	1.64	1.51
4v	2.78±0.32	5.96±0.22	3.01	3.39
4w	7.71±0.23	4.61±0.89	0.35	0.77
4x	12.60±1.78	8.27±1.23	1.60	2.36
Cisplatin^b	3.51±0.14	1.17±0.13	—	—

Compd.	IC_50/(μmol•L^－1)		Lipophilicity factor (ChemOffice)
Compd.	HepG2	MCF-7	log P	Clog P
4a	10.97±3.14	11.05±1.06	2.02	2.21
4b	1.47±0.21	1.56±0.09	2.58	2.93
4c	5.53±0.38	6.05±0.40	2.85	3.08
4d	1.20±0.17	1.74±0.33	2.94	3.10
4e	1.82±0.15	1.27±0.02	2.58	2.93
4f	3.14±0.38	3.15±0.23	2.85	3.08
4g	4.78±1.08	6.05±0.40	2.92	3.24
4h	6.84±0.84	5.91±0.41	1.89	2.13
4i	5.12±0.87	9.96±0.87	2.18	2.36
4j	3.10±0.51	3.71±0.25	2.58	2.93
4k	2.37±0.04	3.30±0.27	2.85	3.08
4l	2.33±0.31	1.23±0.15	2.94	3.10
4m	2.13±0.28	1.06±0.08	0.76	1.96
4n	47.20±2.37	42.18±3.27	1.76	2.22
4o	1.03±0.15	2.48±0.24	2.33	2.50
4p	1.99±0.21	3.65±0.29	3.13	3.64
4q	18.46±1.68	3.40±0.82	2.33	2.50
4r	0.88±0.12	0.80±0.11	3.13	3.64
4s	2.28±0.68	1.20±0.06	3.86	3.98
4t	13.29±2.43	7.32±0.78	3.48	3.71
4u	>50	26.64±4.72	1.64	1.51
4v	2.78±0.32	5.96±0.22	3.01	3.39
4w	7.71±0.23	4.61±0.89	0.35	0.77
4x	12.60±1.78	8.27±1.23	1.60	2.36
Cisplatin^b	3.51±0.14	1.17±0.13	—	—

Compd.	IC_50/(μmol•L^－1)		Lipophilicity factor (ChemOffice)
Compd.	HepG2	MCF-7	log P	Clog P
7a	9.81±0.60	17.16±2.80	3.59	4.73
7b	4.20±0.34	4.28±1.42	3.69	5.10
7c	3.32±0.74	0.83±0.08	3.67	4.94
7d	9.29 0.43	16.65±0.42	4.01	5.29
7e	9.71±0.22	70.28±7.81	5.80	7.12
7f	16.55±1.74	28.65±3.26	2.87	4.08
7g	37.26±2.75	18.56±2.60	3.27	4.22
7h	13.03±1.93	37.51±2.16	3.95	5.28
7i	5.32±0.2273	11.83±1.77	3.69	5.10
Cisplatin^b	3.51±0.14	1.17±0.13	—	—

Compd.	IC_50/(μmol•L^－1)		Lipophilicity factor (ChemOffice)
Compd.	HepG2	MCF-7	log P	Clog P
7a	9.81±0.60	17.16±2.80	3.59	4.73
7b	4.20±0.34	4.28±1.42	3.69	5.10
7c	3.32±0.74	0.83±0.08	3.67	4.94
7d	9.29 0.43	16.65±0.42	4.01	5.29
7e	9.71±0.22	70.28±7.81	5.80	7.12
7f	16.55±1.74	28.65±3.26	2.87	4.08
7g	37.26±2.75	18.56±2.60	3.27	4.22
7h	13.03±1.93	37.51±2.16	3.95	5.28
7i	5.32±0.2273	11.83±1.77	3.69	5.10
Cisplatin^b	3.51±0.14	1.17±0.13	—	—

4-氧代-2-亚胺基噻唑烷-5-亚基乙酸乙酯类化合物的设计、合成及抗癌活性

Design, Synthesis and in vitro Anti-Cancer Activity of Novel Ethyl 4-Oxo-2-iminothiazolidin-5-ylidene Acetates

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