In search of novel anticancer drugs,twenty-one novel longifolene-derived tetraline fused N-acylpyrazole com-pounds 6a～6u were designed and synthesized from renewable natural product longifolene.Their structures were character-ized by FT-IR,NMR,HRMS,and X-ray single-crystal diffraction.The in vitro antiproliferative activity of the target com-pounds 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 4.97μmol/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 antiprolif-erative 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.
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