Design, synthesis and anticancer activity of N-(1-(4-(dibenzo[b,f][1,4]thiazepin-11-yl)piperazin-1-yl)-1-oxo-3-phenylpropan-2-yl derivatives

Bioorg Med Chem Lett. 2017 Sep 1;27(17):4140-4145. doi: 10.1016/j.bmcl.2017.07.029. Epub 2017 Jul 11.

Abstract

Novel N-(1-(4-(dibenzo[b,f][1,4]thiazepin-11-yl)piperazin-1-yl)-1-oxo-3-phenylpropan-2-yl derivatives were designed, synthesized and their chemical structures were confirmed by 1H NMR, 13C NMR and Mass spectra. The anticancer activities of the newly synthesized compounds were evaluated in vitro against three human cancer cell lines including K562, Colo-205 and MDA-MB 231 by MTT assay. The screening results showed that five compounds (16b, 16d, 16i, 16p and 16q) exhibited potent cytotoxic activities with IC50 values between 20 and 40μM. Further in vitro studies revealed that inhibition of sirtuins could be the possible mechanism of action of these molecules.

Keywords: Anticancer activity; Dibenzo[b,f][1,4]thiazepin; Sirtuins; Sunitinib; Synthesis.

MeSH terms

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

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Piperazines
  • Piperazine
  • Sirtuins