Synthesis and antitumor activity of new tetrahydrocurcumin derivatives via click reaction

Three new derivatives of tetrahydrocurcumin 6, 7 and 9 have been prepared as potent antitumor agents using copper(II)-catalyzed 'click chemistry'. Their structures were identified using H-1-NMR, C-13-NMR and HRMS techniques. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay has been carried out to investigate the in vitro cytotoxicity against human cervical carcinoma (HeLa), human lung adenocarcinoma (A549), human hepatoma carcinoma (HepG2) and human colon carcinoma (HCT-116). Compound 6 has showed significant inhibitory activity against HCT-116 cell line with an IC50 value of 17.86 mu M compared to tetrahydrocurcumin (50.96 mu M) and positive control etoposide (19.48 mu M) while showed no inhibitory activity against NCM460 cell line. Compounds 7 showed moderate inhibitory activity compared to tetrahydrocurcumin and etoposide while compound 9 showed no obvious inhibitory activity. The results suggested further structure modifications of tetrahydrocurcumin to improve its anticancer activity.

Automated summary

Three new derivatives of tetrahydrocurcumin were synthesized as potent antitumor agents using 'click chemistry' catalyzed by copper(II), with compound 6 showing significant inhibitory activity against HCT-116 cell line. Further modifications of tetrahydrocurcumin structure are suggested to improve its anticancer activity.