Chinese Journal of Organic Chemistry ›› 2022, Vol. 42 ›› Issue (4): 1129-1135.DOI: 10.6023/cjoc202110025 Previous Articles     Next Articles



朱思玉a, 霍新玉a, 马芹b, 陈伟b, 张洁a,*(), 郭亮a,*()   

  1. a 石河子大学化学化工学院 新疆兵团化工绿色过程重点实验室 新疆石河子 832003
    b 新疆华世丹药物研究有限责任公司 乌鲁木齐 830011
  • 收稿日期:2021-10-18 修回日期:2021-12-23 发布日期:2022-01-11
  • 通讯作者: 张洁, 郭亮
  • 基金资助:
    国家自然科学基金(22067017); 石河子大学创新发展专项(CXFZ201904); 石河子大学高层次人才启动基金(RCZK201933)

Design, Synthesis, and Antitumor Activity of β-Carboline-Benzimidazole Hybrids

Siyu Zhua, Xinyu Huoa, Qin Mab, Wei Chenb, Jie Zhanga(), Liang Guoa()   

  1. a Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, School of Chemistry and Chemical Engineering, Shihezi University, Shihezi, Xinjiang 832003
    b Xinjiang Huashidan Pharmaceutical Research Co, Ltd., Urumqi 830011
  • Received:2021-10-18 Revised:2021-12-23 Published:2022-01-11
  • Contact: Jie Zhang, Liang Guo
  • Supported by:
    National Natural Science Foundation of China(22067017); Project of Innovation and Development from Shihezi University(CXFZ201904); Science Foundation for The Excellent Youth Scholars of Shihezi University(RCZK201933)

In a continuing effort to develop novel β-carboline derivatives endowed with better pharmacological profiles, a series of 1,9-disubstituted β-carboline-benzimidazole hybrids with various substituents were designed and synthesized from L-tryptophan and aldehydes. The target compounds were subjected to antitumor screening against five different cancer cell lines, namely, A549 (lung carcinoma), BGC-823 (gastric carcinoma), CT-26 (murine colon carcinoma), Bel-7402 (liver carcinoma), and MCF-7 (breast carcinoma), using standard methyl thiazolyl tetrazolium (MTT) assay. The structure-activity relationships (SARs) of the conjugates with different substituents at positions 1 and 9 in β-carbolines were also analyzed. The obtained results showed that most conjugates exhibited good cytotoxic activity against more than one cancer cell line. In particular, compound 5s with a benzyl group at position-9 and a trifluoromethyl substituent on the benzimidazole ring had the highest activity against MCF-7 cells (IC50 value of 4.9±0.3 μmol/L). Compounds 5c and 5q displayed significant cytotoxicity against three tumor cell lines, with IC50 values lower than 10 μmol/L. Moreover, these two compounds could moderately reduce the number of migrated cells at concentrations of 2.5~10 μg•mL–1.

Key words: β-carboline, benzimidazole, antitumor, structure-activity relationships