药学学报, 2014, 49(8): 1143-1149
引用本文:
朱齐凤, 龚永祥, 钟金清, 刘礼飞, 李旭飞, 赵旭阳. 新型4-取代-3-硝基苯甲酰胺类似物的设计、合成及活性研究[J]. 药学学报, 2014, 49(8): 1143-1149.
ZHU Qi-feng, GONG Yong-xiang, ZHONG Jin-qing, LIU Li-fei, LI Xu-fei, ZHAO Xu-yang. Design, synthesis and biological evaluation of novel 4-substituted-3-nitrobenzamide derivatives[J]. Acta Pharmaceutica Sinica, 2014, 49(8): 1143-1149.

新型4-取代-3-硝基苯甲酰胺类似物的设计、合成及活性研究
朱齐凤, 龚永祥, 钟金清, 刘礼飞, 李旭飞, 赵旭阳
浙江海正药业股份有限公司, 浙江 台州 318000
摘要:
本文设计合成了系列新型4-取代-3-硝基苯甲酰胺类化合物,并通过1H NMR、13C NMR、MS及元 素分析确证了目标化合物的结构。以HCT-116、MDA-MB435及HL-60三种细胞株为活性筛选对象,利用SRB法进行初步体外抗肿瘤活性研究。结果表明,大部分化合物对于所试验的癌细胞的增殖都有一定程度的抑制作用,其中化合物4a对3种癌细胞的抗增殖作用最显著,GI50为1.904~2.111 μmol·L-1;化合物4g4l4n对MDA-MB435和HL-60的抑制活性较强,其GI50值分别为1.008~3.586 μmol·L-1和1.993~3.778 μmol·L-1,在此基础上初步探讨了此类化合物的构效关系。
关键词:    4-取代-3-硝基苯甲酰胺      合成      抗肿瘤活性      构效关系     
Design, synthesis and biological evaluation of novel 4-substituted-3-nitrobenzamide derivatives
ZHU Qi-feng, GONG Yong-xiang, ZHONG Jin-qing, LIU Li-fei, LI Xu-fei, ZHAO Xu-yang
Zhejiang Hisun Pharmaceutical Co., Ltd., Taizhou 318000, China
Abstract:
A series of novel 4-substituted-3-nitrobenzamide derivatives were designed and synthesized. The structures of the target compounds were confirmed with 1H NMR, 13C NMR, MS and element analysis. Anti-tumor activities against HCT-116, MDA-MB435 and HL-60 cell lines in vitro were evaluated by SRB assay. The results indicated most of the target compounds exhibited potent anti-tumor activity. Compound 4a showed the most potent inhibitory activities against three cancer cell lines with the GI50 values of 1.904-2.111 μmol·L-1. Compounds 4g, 4l-4n exhibited more potent inhibitory activities against MDA-MB435 and HL-60 cell lines with the GI50 values of 1.008-3.586 μmol·L-1 and 1.993-3.778 μmol·L-1, respectively. The structure-activity relationship of these compounds is discussed preliminarily.
Key words:    4-substituted-3-nitrobenzamide    synthesis    anti-tumor activity    structure-activity relationship   
收稿日期: 2014-03-17
通讯作者: 赵旭阳 Tel/Fax:86-576-88828318,E-mail:hisunxyzhao@126.com
Email: hisunxyzhao@126.com
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