Page 125 - 201901

第 36 卷第 1 期 精 细 化 工 Vol.36, No.1
201 9 年 1 月 FINE CHEMICALS Jan. 2019

医药与日化原料
蒎烷基噻唑腙类衍生物的合成及其抗肿瘤活性

2
1
1
匡红波 ，周 慧 ，卞天岑 ，谷 文 1,4 ，朱永强 2,3 ，王石发 1,4*
（1. 南京林业大学 化学工程学院，江苏 南京 210037；2. 南京师范大学 生命科学学院，江苏 南京
210046；3. 江苏正大丰海制药有限公司，江苏 南京 210046；4. 南京林业大学 林业资源高效加工利用
协同创新中心，江苏 南京 210037）

1
摘要：以诺蒎酮为原料，经过加成、缩合、环化等反应，合成出蒎烷基噻唑腙衍生物 4a~4n，采用 FTIR、HNMR、
13 CNMR 和 HRMS 对化合物的结构进行了表征。考察了化合物 4a~4n 对人肝癌细胞（HepG2）、人多发性骨髓瘤
细胞（RPMI-8226）、人肺癌细胞（A549）和乳腺癌细胞（MDA-MB-231）的抗肿瘤活性。实验结果表明，化合
物 4a 的抗肿瘤活性最强，其对 HepG2、8226、A549 和 231 细胞的 IC 50 分别低至 5.8、8.8、7.1 和 10.6 μmol/L；化
合物 4c 的抗肿瘤活性也较强，其 IC 50 分别为 8.9、8.7、7.3 和 9.7 μmol/L。细胞凋亡和周期实验数据显示，当化合
物 4a 浓度从 0 增加到 40 μmol/L 时，A549 细胞的总凋亡率从 6.55%增加到 47.20%，G2/M 期的细胞数量从 13.50%
上升至 51.72%。以上结果表明，化合物 4a 能够诱导 A549 细胞凋亡，并将细胞有丝分裂周期阻滞在 G2/M 期。
关键词：诺蒎酮；蒎烷基噻唑腙；抗肿瘤活性；细胞凋亡；细胞周期；医药与日化原料
中图分类号：O622.6 文献标识码：A 文章编号：1003-5214 (2019) 01-0111-08

Synthesis and Antitumor Activity of Pinanyl
Thiazole Hydrazone Derivatives

1
2
1,4
1
KUANG Hong-bo , ZHOU Hui , BIAN Tian-cen , GU Wen ,
2,3
ZHU Yong-qiang , WANG Shi-fa 1,4*
（1. College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, Jiangsu, China; 2. College of Life
Science, Nanjing Normal University, Nanjing 210046, Jiangsu, China; 3. Jiangsu Chia Tai Fenghai Pharmaceutical Co. Ltd.,
Nanjing 210046, Jiangsu, China; 4. Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources,
Nanjing Forestry University, Nanjing 210037, Jiangsu, China）
Abstract: Pinanyl thiazole hydrazone derivatives 4a~4n were synthesized from nopinone via addition,
13
1
condensation and cyclization, and their structures were characterized by FTIR, HNMR, CNMR and
HRMS. The antitumor activities of compounds 4a~4n against four human cancer cell lines including
HepG2, RPMI-8226, A549 and MDA-MB-231 were evaluated in vitro. The results showed that compound
4a had the best antitumor activity against the above four cancer cell lines, the IC 50 values against HepG2,
RPMI-8226, A549 and MDA-MB-231 were as low as 5.8, 8.8, 7.1 and 10.6 μmol/L, respectively. Compound
4c also had stronger activity with the corresponding IC 50 values of 8.9, 8.7, 7.3 and 9.7 μmol/L. Cell
apoptosis and cell cycle experiments indicated that when the concentration of compound 4a increased from
0 to 40 μmol/L, the total apoptotic rate of A549 cells increased from 6.55% to 47.20%, and the number of
cells in G2/M phase increased from 13.50% to 51.72%. It was found that compound 4a could induce
apoptosis in A549 cells in a dose-dependent manner and arrest the cell cycle at the G2/M phase.
Key words: nopinone; pinanyl thiazole hydrazone; antitumor activity; cell apoptosis; cell cycle; drug and
cosmetic materials
Foundation items: National Natural Science Foundation of China (31470592); Major Project of Jiangsu
Province University Natural Science (14KJ220001)

收稿日期：2018-04-25; 定用日期：2018-09-25; DOI: 10.13550/j.jxhg.20180303
基金项目：国家自然科学基金（31470592）；江苏省高校自然科学研究重大项目（14KJ220001）
作者简介：匡红波（1992—），男，硕士生。联系人：王石发（1965—），男，教授，电话：025-85428369，E-mail：wangshifa65@163.com。