Synthesis and antitumor activity of new tetrahydrocurcumin derivatives via click reaction

Abstract

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 ¹H-NMR, ¹³C-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 μM compared to tetrahydrocurcumin (50.96 μM) and positive control etoposide (19.48 μM) 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.

Keywords:

• Tetrahydrocurcumin
• podophyllotoxin
• click reaction
• antitumor activity
• drug discovery

Disclosure statement

No potential conflict of interest was reported by authors.

Additional information

Funding

This work was financially supported by Natural Science Foundation of Guangdong Province (Grant No. 2017A030313775, Grant No. 2019A1515011822). Ahmed Mahal acknowledges the Chinese Academy of Sciences (CAS) for support through the CAS President’s International Fellowship Initiative (2016PM032) and Cihan University as well.