Rui Xie

The stability and degradation mechanism of sulforaphene in solvents

Sulforaphene, a natural compound, has been investigated as a potential anticancer agent. However, the stability of sulforaphene, in various solvents, and its degradation pathway have not been appropriately reported. This instability impairs the preparation process, the biological evaluation experiments, and the applications of sulforaphene. In this study, the stability of sulforaphene stored at 26°C was investigated in each of the following six solvents: two kinds of protic solvents (methanol and ethanol) and four kinds of aprotic solvents (acetonitrile, dichloromethane, ethyl acetate and acetone). Sulforaphene was found to be stable in aprotic solvents and unstable in the protic solvents. The degradation products of sulforaphene in protic solvents (methanol and ethanol) were purified by the preparative HPLC and identified by ESI/MS and NMR ((1)H NMR). The degradation pathways of sulforaphene in methanol and ethanol were proposed. It was found that sulforaphene was degraded into two kinds of structural isomer in alcohols.

Rational design, synthesis and preliminary antitumor activity evaluation of a chlorambucil derivative with potent DNA/HDAC dual-targeting inhibitory activity

Histone deacetylases (HDACs) play a pivotal role not only in gene expression but also in DNA repair. Herein, we report the successful design, synthesis and evaluation of a chlorambucil derivative named vorambucil with a hydroxamic acid tail as a DNA/HDAC dual-targeting inhibitor. Vorambucil obtained both potent DNA and HDACs inhibitory activities. Molecular docking results supported the initial pharmacophoric hypothesis and rationalized the potent inhibitory activity of vorambucil against HDAC1, HDAC2 and HDAC6. Vorambucil showed potent antiproliferative activity against all the test four cancer cell lines with IC50 values of as low as 3.2-6.2μM and exhibited 5.0-18.3-fold enhanced antiproliferative activity than chlorambucil. Vorambucil also significantly inhibits colony formation of A375 cancer cells. Further investigation showed that vorambucil remarkably induced apoptosis and arrested the cell cycle of A375 cells at G2/M phase. Vorambucil could be a promising candidate and a useful tool to elucidate the role of those DNA/HDAC dual-targeting inhibitors for cancer therapy.

Synergistic Effect of the Combination of Novel Suberoylanilide Hydroxamic Acid Derivatives with Cisplatin on Anti-proliferation of Human Cancer Cells

A novel, green, and atom-economical boric acid catalyzed direct amidation without the use of any coupling agents for the preparation of suberoylanilide hydroxamic acid (SAHA) and SAHA-based inhibitors targeting anti-proliferation of cancer cells is provided. The new SAHA-based inhibitor B123, when used alone, exhibited higher anti-proliferative activities than SAHA or Cisplatin against a number of human cancer cells. We have examined the effect of combination of these SAHA-based inhibitors with Cisplatin. We found synergistic effects of the combination of SAHA-based inhibitors with Cisplatin over a wide range of concentrations against human liver cancer cells HepG2 and two human lung cancer cell lines H1299 and H460. This synergism leads up to 8-fold of dose reduction for Cisplatin in the combination with our synthesized inhibitor B123 against H1299.