Synthesis, molecular modeling and biological evaluation of 2-aminomethyl-5-(quinolin-2-yl)-1,3,4-oxadiazole-2(3H)-thione quinolone derivatives as novel anticancer agent

Eur J Med Chem. 2013 Feb:60:23-8. doi: 10.1016/j.ejmech.2012.11.039. Epub 2012 Dec 4.

Abstract

A series of quinoline derivatives (4a-4o) have been synthesized and their biological activities were also evaluated as potential telomerase inhibitors. Bioassay tests demonstrated that most of the compounds exhibited substantial broad-spectrum antitumor activity against the three cancer cell lines (HepG2, SGC-7901 and MCF-7). Moreover, all the title compounds were assayed for telomerase inhibition using the TRAP-PCR-ELISA assay. Compounds 4d and 4i displayed the most potent anticancer activities, which were comparable to the positive control. Docking simulation was performed to position compounds 4d and 4i into the telomerase structure active site to determine the probable binding model. Compounds 4d and 4i with potent inhibitory activity in tumor growth inhibition may be potential anticancer agents.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Oxadiazoles / chemical synthesis*
  • Oxadiazoles / chemistry
  • Oxadiazoles / pharmacology*
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • Structure-Activity Relationship
  • Telomerase / antagonists & inhibitors
  • Telomerase / metabolism

Substances

  • 3-(((2-fluorophenyl)amino)methyl)-5-(quinolin-2-yl)-1,3,4-oxadiazole-2(3H)-thione
  • 3-(((4-chlorophenyl)amino)methyl)-5-(quinolin-2-yl)-1,3,4-oxadiazole-2(3H)-thione
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Oxadiazoles
  • Quinolines
  • Telomerase