Computer-aided drug design and inhibitive effect of a novel nitrogenous heterocyclic compound and its mechanism on glioma U251 cells and breast cancer MCF-7 cells

Drug Des Devel Ther. 2018 Jun 27:12:1931-1939. doi: 10.2147/DDDT.S168130. eCollection 2018.

Abstract

Background: Glioma and breast cancer are severe malignant cancerous tumors that highlight the importance of developing new anti-cancer drugs. The aim of this study was to explore the effects of a novel nitrogenous heterocyclic compound on glioma and breast cancer cells and to determine its mechanism of action.

Methods: We designed and synthesized a novel nitrogenous heterocyclic compound, 3-(4-amino-1H-benzo[d]imidazole-2-carboxamido)-4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5] tetrazine-8-carboxamide, based on alkylglycerone phosphate synthase (AGPS) using computer-aided drug design (CADD), and we measured its effect on the proliferation, invasion, cell cycle and apoptosis of U251 glioma and MCF-7 breast cancer cells. In addition, the compound's effect on the expression of tumor-related mRNA, circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) was explored.

Results: It was found that the nitrogenous heterocyclic compound could induce cell cycle arrest at the G2/M phase of U251/MCF-7 cells and activate apoptosis. Real-time PCR showed that the expression levels of tumor-related mRNA, circRNAs and lncRNAs were impacted.

Conclusion: We concluded that the nitrogenous heterocyclic compound inhibits the proliferation and invasion of U251 glioma and MCF-7 breast cancer cells through the induction of apoptosis and cell cycle arrest by regulating tumor-related genes.

Keywords: breast cancer; glioma; invasion; nitrogenous heterocyclic compound; proliferation.

MeSH terms

  • Alkyl and Aryl Transferases / genetics
  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Design*
  • Glioma / drug therapy*
  • Glioma / pathology
  • Heterocyclic Compounds / chemical synthesis*
  • Heterocyclic Compounds / pharmacology
  • Humans
  • MCF-7 Cells
  • Rats

Substances

  • Antineoplastic Agents
  • Heterocyclic Compounds
  • Alkyl and Aryl Transferases
  • alkylglycerone-phosphate synthase