Synthesis and biochemical studies of novel organic selenides with increased selectivity for hepatocellular carcinoma and breast adenocarcinoma

Eur J Med Chem. 2019 Oct 1:179:515-526. doi: 10.1016/j.ejmech.2019.06.075. Epub 2019 Jun 28.

Abstract

Nineteen organoselenides were synthesized and tested for their intrinsic cytotoxicity in hepatocellular carcinoma (HepG2) and breast adenocarcinoma (MCF-7) cell lines and their corresponding selective cytotoxicity (SI) was estimated using normal lung fibroblast (WI-38) cells. Most of the organic selenides exhibited good anticancer activity, and this was more pronounced in HepG2 cells. Interestingly, the naphthoquinone- (5), thiazol- (12), and the azo-based (13) organic selenides demonstrated promising SI (up to 76). Furthermore, the amine 4c, naphthoquinone 5, and azo-based 13 and 15 organic selenides were able to down-regulate the expression of Bcl-2 and up-regulate the expression levels of IL-2, IL-6 and CD40 in HepG2 cells compared to untreated cells. Moreover, most of the synthesized candidates manifested good free radical-scavenging and GPx-like activities comparable to vitamin C and ebselen. The obtained results suggested that some of the presented organoselenium candidates have promising anti-HepG2 and antioxidant activities.

Keywords: Antioxidant; Azo coupling; Breast adenocarcinoma; Diselenides; Hepatocellular carcinoma; Michael-type reaction; Selenides; Selenocyanates.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antioxidants / chemical synthesis
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Biphenyl Compounds / antagonists & inhibitors
  • Biphenyl Compounds / metabolism
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Line
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Female
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • MCF-7 Cells
  • Molecular Structure
  • Organoselenium Compounds / chemical synthesis
  • Organoselenium Compounds / chemistry
  • Organoselenium Compounds / pharmacology*
  • Picrates / antagonists & inhibitors
  • Picrates / metabolism
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Antioxidants
  • Biphenyl Compounds
  • Organoselenium Compounds
  • Picrates
  • 1,1-diphenyl-2-picrylhydrazyl