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).

Novel 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 as PowerPoint slide