New benzothieno[3,2-d]-1,2,3-triazines with antiproliferative activity: synthesis, spectroscopic studies, and biological activity

Bioorg Med Chem Lett. 2014 Aug 1;24(15):3291-7. doi: 10.1016/j.bmcl.2014.06.007. Epub 2014 Jun 17.

Abstract

New benzothieno[3,2-d]-1,2,3-triazines, together with precursors triazenylbenzo[b]thiophenes, were designed, synthesized and screened as anticancer agents. The structural features of these compounds prompted us to investigate their DNA binding capability through UV-vis absorption titrations, circular dichroism, and viscometry, pointing out the occurrence of groove-binding. The derivative 3-(4-methoxy-phenyl)benzothieno[3,2-d]-1,2,3-triazin-4(3H)-one showed the highest antiproliferative effect against HeLa cells and was also tested in cell cycle perturbation experiments. The obtained results assessed for the first time the anticancer activity of benzothieno[3,2-d]-1,2,3-triazine nucleus, and we related it to its DNA-binding properties.

Keywords: Antiproliferative activity; Benzothienotriazines; Cell-cycle analysis; Spectroscopic studies; VLAK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • Circular Dichroism
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • HeLa Cells
  • Humans
  • Molecular Structure
  • Spectrophotometry, Ultraviolet
  • Structure-Activity Relationship
  • Thiophenes / chemical synthesis
  • Thiophenes / chemistry
  • Thiophenes / pharmacology*
  • Triazines / chemical synthesis
  • Triazines / chemistry
  • Triazines / pharmacology*
  • Viscosity

Substances

  • 3-(4-methoxyphenyl)benzothieno(3,2-d)-1,2,3-triazin-4(3H)-one
  • Antineoplastic Agents
  • Thiophenes
  • Triazines