Design, synthesis, molecular docking and anti-hepatocellular carcinoma evaluation of novel acyclic pyridine thioglycosides

Nucleosides Nucleotides Nucleic Acids. 2018 Mar 4;37(3):186-198. doi: 10.1080/15257770.2018.1450508. Epub 2018 Apr 2.

Abstract

A novel series of acyclic pyridine thioglycosides has been synthesized. Evaluation of the anti proliferative activity of these compounds against HEPG-2 cell lines (liver carcinoma cell lines) shows that most of the compounds have high anti-tumor activities especially 6b, 6c, 7b and 7c. Furthermore, in the modeling study, these compounds showed that they have high binding affinity with thymidylate synthase dihydrofolate reductase (TS-DHFR).

Keywords: Acyclic pyridine thioglycosides; anti-tumor activity; cytotoxic activity; docking studies; thioglycosides; thymidylate synthase dihydrofolate reductase (TS-DHFR).

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / therapeutic use
  • Binding Sites
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • Cell Survival / drug effects
  • Drug Design
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Molecular Docking Simulation
  • Molecular Structure
  • Multienzyme Complexes / metabolism
  • Protein Binding
  • Pyridines / chemical synthesis*
  • Pyridines / therapeutic use
  • Structure-Activity Relationship
  • Tetrahydrofolate Dehydrogenase / metabolism
  • Thioglycosides / chemical synthesis*
  • Thioglycosides / therapeutic use
  • Thymidylate Synthase / metabolism

Substances

  • Antineoplastic Agents
  • Multienzyme Complexes
  • Pyridines
  • Thioglycosides
  • thymidylate synthase-dihydrofolate reductase
  • Tetrahydrofolate Dehydrogenase
  • Thymidylate Synthase