Synthesis and Antiproliferative Activity Evaluation of Novel Glaucocalyxin A-1,2,3-Triazole Derivatives

A series of novel 1,2,3-triazole derivatives based on natural product glaucocalyxin A (GLA) were designed and prepared. Their antiproliferative activity was evaluated against six human tumor cell lines (HepG2, NCI-H460, JEG-3, K562, HL-60, Hela). Most compounds exhibited potent antiproliferative effects with low micromolar IC50 values. The activity of some of the compounds is significantly superior to GLA. In particular, (3S,3aR,3a1R,6aR,11aR)-5-(1-(4-hydroxyphenyl)-1H1,2,3-triazol-4-yl)-8,8,11a-trimethyl-13-methylenedecahy-dro-1H-3,3a1-ethanophenanthro[1,10-de][1,3]dioxine-9,12(2H)-dione (16) displayed the highest inhibition efficacy (IC50=0.25 mu mol(.)L(-1)), which was 6.9 times higher than that of the positive control adriamycin and 25.8 times higher than that of GLA against HL-60 cells. The results also demonstrated that the introduction of triazole acetal with meta- and para-hydroxyl substitution on phenyl without change of methylene cyclopentanone on the D-ring could improve the antitumor activity of GLA significantly. The apoptosis morphology and flow cytometry studies indicated that the triazole-fused GLA derivatives could induce apoptosis of tumor cells.

Automated summary

A series of novel 1,2,3-triazole derivatives based on natural product GLA were designed and prepared, showing potent antiproliferative activity against human tumor cell lines. Some compounds exhibited higher activity than GLA. The introduction of specific structures significantly improved the antitumor activity of GLA, and the derivatives were found to induce apoptosis of tumor cells.