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

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 IC 50 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 IC 50 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 IC 50 values of 8.88, 9.47 and 9.99 µM, respectively. Compounds 3e, 2e and 3c revealed effective biological potency on HT29 cells with IC 50 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.

Design, Synthesis and Biological Evaluation of Glycosylated Derivatives of Silibinin as Potential Anti-Tumor Agents

“…Silymarin is a representative extract derived from the seeds of milk thistle (Silybum marianum), which consists of several flavonoid lignin-like compounds (silibinin, isosilybin and silychristin) (Figure 1). [1][2][3][4] Silibinin, the most abundant active ingredient of silymarin, exhibits a variety of characteristics in terms of therapeutic activities, including antioxidant, free radicals scavenging, maintaining the stability of cell membrane, promoting hepatocyte proliferation and reducing blood lipids. 5,6 Several animal studies in vivo have confirmed that silibinin possesses a significant inhibitory effect on different types of tumors including liver, colon, prostate, bladder and tongue through the suppression of receptor tyrosine kinase (RTK) represented by epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF-1R) and the activation of downstream signaling molecules.…”

Efficient synthesis and biological evaluation of some new series of pyridine derivatives: Promising and potent new class of anticancer agents

“…Overall, 28.4 million new cancer cases are expected in 2040, a 47% increase from 19.3 million in 2020, assuming local rates remain stable in 2020. [ 1–3 ] Heterocyclic systems that containing nitrogen have a great importance because of their vital role in biological systems [ 4 ] recently, different heterocyclic nitrogen rings have shown very complex biological properties that making them one of the most important groups in the medicinal chemistry molecules. [ 5 ] Among these heterocycles, pyridine is the simplest one of the azine type.…”