Chinese Journal of Organic Chemistry ›› 2024, Vol. 44 ›› Issue (1): 232-241.DOI: 10.6023/cjoc202305025 Previous Articles     Next Articles



王博珍a,b, 张婕b, 粘春惠b, 金茗茗b, 孔苗苗c, 李物兰c, 何文斐b,*(), 吴建章a,b,*()   

  1. a 温州医科大学附属眼视光医院 浙江温州 325027
    b 温州医科大学药学院 浙江温州 325035
    c 温州医科大学附属第一医院 浙江温州 325035
  • 收稿日期:2023-05-18 修回日期:2023-08-16 发布日期:2023-09-15
  • 作者简介:
  • 基金资助:
    浙江省自然科学基金(LGF20B020001); 浙江省自然科学基金(LGF21H160034); 国家自然科学基金(81903074)

Synthesis and Antitumor Activity of 3,4-Dichlorophenyl Amides

Bozhen Wanga,b, Jie Zhangb, Chunhui Nianb, Mingming Jinb, Miaomiao Kongc, Wulan Lic, Wenfei Heb(), Jianzhang Wua,b()   

  1. a The Eye Hospital, School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, Zhejiang 325027
    b School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035
    c The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035
  • Received:2023-05-18 Revised:2023-08-16 Published:2023-09-15
  • Contact: *E-mail:; E-mail:
  • About author:
    These authors contributed equally to this work.
  • Supported by:
    Natural Science Foundation of Zhejiang Province(LGF20B020001); Natural Science Foundation of Zhejiang Province(LGF21H160034); National Natural Science Foundation of China(81903074)

In order to find efficient antitumor compounds, 19 novel 3,4-dichlorophenyl amides were designed and synthesized by introducing amide bonds and 3,4-dichloro substitution into the curcumin skeleton according to the principles of medicinal chemistry combination. The in vitro antitumor activity of the compounds against AGS and BGC-823 gastric cancer cells were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The results showed that some compounds displayed potential inhibitory activity. Notably, (2E)-3-(3,4-dichlorophenyl)-1-(2-(3-(4-(trifluoromethyl)phenyl)propio- nyl)ethylazo)propan-2-en-1-one (17) showed potent growth inhibition on AGS with a half maximal inhibitory concentration (IC50) value of (1.94±0.94) μmol/L. Besides, the results of cell colony formation, wound healing, flow cytometry and western blot showed that compound 17 significantly inhibited the growth and migration of AGS cells, arrested the cell cycle in G0/G1 phase, and induced a dose-dependent up-regulation of the pro-apoptotic proteins such as cleaved poly ADP-ribose polymerase (Cleaved-PARP) and Bcl2-associated X protein (Bax), and a down-regulation of the anti-apoptotic protein Bcl-2, thus inducing cell apoptosis. Preliminary mechanistic studies suggested that compound 17 may exert its anti-gastric cancer effects in vitro by inhibiting dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A)-protein kinase B (PKB, AKT) signaling pathway. In conclusion, this study indicates that amide compounds containing 3,4-dichlorophenyl may be a class of small molecule compounds with promising prospects for medicinal research, and compound 17 is expected to be an antitumor candi-date.

Key words: curcumin analog, 3,4-dichlorophenyl, amide bond, synthesis, antitumor activity