Chinese Journal of Organic Chemistry ›› 2024, Vol. 44 ›› Issue (6): 1967-1977.DOI: 10.6023/cjoc202312015 Previous Articles     Next Articles

ARTICLES

新型长叶烯基萘满并N-酰基吡唑化合物的合成、抗增殖活性、三维定量构效关系及分子对接研究

秦丽清a,b, 林桂汕a,b,*(), 段文贵a,b,*(), 崔玉成a,b, 杨卯芳a,b, 李芳耀c, 李典鹏d   

  1. a 广西大学化学化工学院 南宁 530004
    b 广西高校应用化学技术与资源开发重点实验室 南宁 530004
    c 桂林医学院药学院 广西桂林 541100
    d 广西植物功能物质与资源持续利用重点实验室 广西桂林 541006
  • 收稿日期:2023-12-16 修回日期:2024-01-23 发布日期:2024-02-27
  • 基金资助:
    国家自然科学基金(32260366); 国家自然科学基金(32360360); 广西植物功能物质研究与利用重点实验室基金(FPRU2020-3)

Synthesis, Antiproliferative Activity, 3D-QSAR and Molecular Docking Study of Novel Longifolene-Derived Tetraline Fused N-Acyl-pyrazole Compounds

Liqing Qina,b, Guishan Lina,b,*(), Wengui Duana,b,*(), Yucheng Cuia,b, Maofang Yanga,b, Fangyao Lic, Dianpeng Lid   

  1. a School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004
    b Guangxi Colleges and Universities Key Laboratory of Applied Chemistry Technology and Resource Development, Nanning 530004
    c College of Pharmacy, Guilin Medical University, Guilin, Guangxi 541100
    d Guangxi Key Laboratory of Functional Phytochemicals Research and Utilization, Guilin, Guangxi 541006
  • Received:2023-12-16 Revised:2024-01-23 Published:2024-02-27
  • Contact: * E-mail: gslin@gxu.edu.cn; wgduan@gxu.edu.cn
  • Supported by:
    National Natural Science Foundation of China(32260366); National Natural Science Foundation of China(32360360); Fund of Guangxi Key Laboratory of Functional Phytochemicals Research and Utilization(FPRU2020-3)

In search of novel anticancer drugs, twenty-one novel longifolene-derived tetraline fused N-acylpyrazole compounds 6a~6u were designed and synthesized from renewable natural product longifolene. Their structures were characterized by FT-IR, NMR, HRMS, and X-ray single-crystal diffraction. The in vitro antiproliferative activity of the target compounds was evaluated by the methylthiazolyldiphenyl-tetrazolium bromide (MTT) method. As a result, some of the target compounds showed better antiproliferative activity than that of the positive control fluorouracil (5-FU). Among these, 4-(7-isopropyl-5,5-dimethyl-4,5-dihydro-2H-benzo[g]indazole-2-carbonyl)benzonitrile (6r) (R=p-CNC6H4) had IC50 of 4.97 μmol/L against SW480 cell (human colon cancer cell), and (7-isopropyl-5,5-dimethyl-4,5-dihydro-2H-benzo[g]indazol-2-yl)-(4-nitrophenyl) methanone (6q) (R=p-NO2C6H4) had IC50 of 8.02 μmol/L against MCF-7 cell (human breast cancer cell), exhibiting significant antiproliferative activity. Compound 6q (R=p-NO2C6H4) displayed good and broad-spectrum antiproliferative activity, with IC50 of 10.97, 11.95, 19.78, 20.15 and 23.45 μmol/L against MCF-7 cell, MGC-803 cell (human gastric cancer cell line), HepG2 cell (human hepatocellular carcinoma cell), Hela cell (human cervical cancer cell), and A549 cell (human lung adenocarcinoma cell), respectively. Furthermore, the relationship between structures and their antiproliferative activity was investigated by the established 3D-quantitative structure-activity relationship (3D-QSAR) model (r2=0.986 and q2=0.631), and the interaction mode between the target compounds and Survivin was also simulated by molecular docking.

Key words: longifolene-derived tetraline, N-acyl-pyrazole, synthesis, antiproliferative activity, 3D-quantitative structure- activity relationship (3D-QSAR), molecular docking