新颖的2,6-二氯-3,5-二硝基甲苯衍生物的设计, 合成及抗肿瘤活性的评价

doi:10.5246/jcps.2018.03.017

中国药学(英文版) ›› 2018, Vol. 27 ›› Issue (3): 159-169.DOI: 10.5246/jcps.2018.03.017

新颖的2,6-二氯-3,5-二硝基甲苯衍生物的设计, 合成及抗肿瘤活性的评价

焦佳媛¹, 胡浩², 魏思源¹, 王婉秋¹, 林鹤³, 柴宝山^1*

1. 沈阳化工研究院有限公司医药研究室, 辽宁沈阳 110021
2. 沈阳药科大学, 辽宁沈阳 110016
3. 沈阳化工研究院有限公司安评中心, 辽宁沈阳 110021

收稿日期:2017-12-19 修回日期:2018-01-09 出版日期:2018-03-31 发布日期:2018-03-13
通讯作者: Tel.: +86-024-85869191, E-mail: chaibaoshan@sinochem.com
基金资助:
The Natural Science Foundation of Liaoning province (Grant No. 20170540730).

Design, synthesis and antitumor activity evaluation of novel 2,6-dichloro-3,5-dinitrotoluene derivatives

Jiayuan Jiao¹, Hao Hu², Siyuan Wei¹, Wanqiu Wang¹, He Lin³, Baoshan Chai^1*

1. Pharmaceutical Research Laboratory, Shenyang Research Institute of Chemical Industry Co., Ltd., Shenyang 110021, China
2. Shenyang Pharmaceutical University, Shenyang, 110016, China
3. Safety Evaluation Center, Shenyang Research Institute of Chemical Industry Co., Ltd, Shenyang 110021, China

Received:2017-12-19 Revised:2018-01-09 Online:2018-03-31 Published:2018-03-13
Contact: Tel.: +86-024-85869191, E-mail: chaibaoshan@sinochem.com
Supported by:
The Natural Science Foundation of Liaoning province (Grant No. 20170540730).

摘要/Abstract

摘要：

本文设计、合成了一系列结构新颖的2,6-二氯-3,5-二硝基甲苯衍生物, 并且评价了它们对五种细胞系(A431, HepG2, A549, HT-29和HEK-293)的活性。与顺铂相比, 大多数化合物对一种或多种细胞系表现出中等或者显著性的细胞毒性及高选择性。对其构效关系(SARs)初步的研究表明, 含有苯基(1-哌嗪基)甲酮基团的化合物, 特别是在苯环4位氯原子取代的化合物具有更高的活性。发现化合物4g是最有潜力的衍生物, 其对A431, Hep G2, A549, HT-29和HEK-293细胞的IC₅₀分别为1.04, 3.20, 6.93, 4.10和20.15 μmol/L, 其活性结果优于在临床上使用最广泛的化疗药物之一的阳性药顺铂。

关键词: 2,6-二氯3,5-二硝基甲苯, 细胞毒活性, 构效关系

Abstract:

A series of novel 2,6-dichloro-3,5-dinitrotoluene derivatives were designed, synthesized in the present study, and their antitumor activities against five cell lines (A431, HepG2, A549, HT-29 and HEK-293) were tested. Most of the compounds exhibited moderate-to-significant cytotoxicity and high selectivity against one or more cell lines in comparison with cisplatin. Studies on their preliminary structure-activity relationships (SARs) indicated that compounds containing phenyl (piperazin-1-yl) methanone groups, especially chlorine atom at 4-position of the phenyl ring, were more effective. Compound 4g was found to be the most potent derivative with IC₅₀values of 1.04, 3.20, 6.93, 4.10 and 20.15 μmol/L against A431, Hep G2, A549, HT-29 and HEK-293 cell lines, respectively, which was better than positive control cisplatin, one of the most clinically used chemotherapeutic drugs.

Key words: 2,6-Dichloro-3,5-dinitrotoluene, Cytotoxic activity, Structure-activity relationships

中图分类号:

R916

Supporting:

焦佳媛, 胡浩, 魏思源, 王婉秋, 林鹤, 柴宝山. 新颖的2,6-二氯-3,5-二硝基甲苯衍生物的设计, 合成及抗肿瘤活性的评价[J]. 中国药学(英文版), 2018, 27(3): 159-169.

Jiayuan Jiao, Hao Hu, Siyuan Wei, Wanqiu Wang, He Lin, Baoshan Chai. Design, synthesis and antitumor activity evaluation of novel 2,6-dichloro-3,5-dinitrotoluene derivatives[J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(3): 159-169.

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新颖的2,6-二氯-3,5-二硝基甲苯衍生物的设计, 合成及抗肿瘤活性的评价

Design, synthesis and antitumor activity evaluation of novel 2,6-dichloro-3,5-dinitrotoluene derivatives

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