Design and stereoselective synthesis of novel isosteviol-fused pyrazolines and pyrazoles as potential anticancer agents

•Two series of novel heterocycle fused with isosteviol derivatives were synthesized.•Cytotoxic activities of sixty analogs of isosteviol were tested in vitro.•Compound 11t showed the highest cytotoxities (IC50: 2.71, 3.18, 1.09 and 13.52 μM).•The structure–activity relationships of the isosteviol analogs were discussed.

Two series of novel isosteviol-fused pyrazoline and pyrazole derivatives were facilely synthesized via intramolecular 1,3-dipolar cycloaddition and condensation reaction, respectively. All compounds were characterized by NMR, IR and HRMS spectra. The stereochemistry of compounds 9b, 10, 11a and 11v were further confirmed by X-ray crystallographic analysis. The antiproliferative activities of the structurally related pyrazoline and pyrazole derivatives were tested in vitro on four human malignant cell lines (SGC 7901, A549, Raji and HeLa): Our results revealed that isosteviol-fused pyrazole derivatives exhibited noteworthy cytotoxic activities. Among them, 2,4-di-Cl-phenylpyrazole derivative 11t displayed better cytotoxities with IC50 values: 2.71, 3.18, 1.09 and 13.52 μM against SGC 7901, A549, Raji and HeLa, respectively, compared to cisplatin (IC50 values: 7.56, 17.78, 17.32 and 14.31 μM, respectively).

Graphical abstractNovel isosteviol-fused pyrazoline and pyrazole derivatives were facilely prepared. Compounds 11t displayed noteworthy cytotoxities (IC50 = 2.71, 3.18, 1.09 and 13.52 μM) against SGC 7901, A549, Raji and HeLa, respectively.Figure optionsDownload full-size imageDownload as PowerPoint slide