1. Academic Validation
  2. Synthesis and antitumor activity of novel silibinin and 2,3-dehydrosilybin derivatives with carbamate groups

Synthesis and antitumor activity of novel silibinin and 2,3-dehydrosilybin derivatives with carbamate groups

  • Med Chem Res. 2022;31(4):533-544. doi: 10.1007/s00044-022-02854-6.
Qiuchan Wu  # 1 Jiang Zeng  # 2 Jinfu Dong  # 3
Affiliations

Affiliations

  • 1 Department of Hematology and Medical Oncology, Tianjin Fifth Central Hospital, Tianjin, 300450 China.
  • 2 Department of Pharmacy, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, 545005 China.
  • 3 Department of Medicinal Chemistry, Central South University, No. 172 Tongzipo Road, Changsha, Hunan 410013 China.
  • # Contributed equally.
Abstract

A novel series of silibinin and 2,3-dehydrosilybin derivatives bearing carbamate groups were designed, synthesized and their in vitro Anticancer activities were screened against human Cancer cell lines including MCF-7, NCI-H1299, HepG2 and HT29 by CCK-8 assay. The results showed that most of the compounds significantly suppressed the proliferation of tested Cancer cells. Among them, compounds 2h, 3h and 3f demonstrated markedly higher antiproliferative activity on MCF-7 cells with IC50 values of 2.08, 5.54 and 6.84 µM, respectively. Compounds 3e, 3g and 2g displayed better cytotoxic activity against NCI-H1299 cells with IC50 values of 8.07, 8.45 and 9.09 µM, respectively. Compounds 3g, 3c and 3h exhibited a promising inhibitory effect against HepG2 cells with IC50 values of 8.88, 9.47 and 9.99 µM, respectively. Compounds 3e, 2e and 3c revealed effective biological potency on HT29 cells with IC50 values of 6.27, 9.13 and 9.32 µM, respectively. In addition, the outcomes of the docking studies between compounds 2f, 2h, 3e, 3g and HSP90 receptor (PDB ID: 4AWO) suggest the possible mechanism of inhibition against MCF-7 cell lines. Graphical abstract.

Keywords

2,3-dehydrosilybin; Anticancer; Carbamate; Docking; Silibinin; Synthesis.

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