Chinese Journal of Organic Chemistry >
Synthesis, Antiproliferative Activity, 3D-QSAR and Molecular Docking Study of Novel Longifolene-Derived Tetraline Fused N-Acyl-pyrazole Compounds
Received date: 2023-12-16
Revised date: 2024-01-23
Online published: 2024-02-28
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.
Liqing Qin , Guishan Lin , Wengui Duan , Yucheng Cui , Maofang Yang , Fangyao Li , Dianpeng Li . Synthesis, Antiproliferative Activity, 3D-QSAR and Molecular Docking Study of Novel Longifolene-Derived Tetraline Fused N-Acyl-pyrazole Compounds[J]. Chinese Journal of Organic Chemistry, 2024 , 44(6) : 1967 -1977 . DOI: 10.6023/cjoc202312015
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