Synthesis and Biological Evaluation of Novel 1,3,4-thiadiazole Derivatives Incorporating Benzisoselenazolone Scaffold as Potential Antitumor Agents

Med Chem. 2016;12(7):631-639. doi: 10.2174/1573406412666160201120806.

Abstract

Background: Based on the biological significance of benzisoselenazolone and 1,3,4-thiadiazole, a series of novel 1,3,4-thiadiazole derivatives incorporating benzisoselenazolone scaffold were designed and synthesized with ebselen as a lead compound.

Methods: Meanwhile, their in vitro antitumor activities were evaluated against SMMC-7721, MCF-7 and A549 human cancer cell lines by CCK-8 assay.

Results: The preliminary bioassay results demonstrated that all tested compounds 4a-q showed potent antitumor activities, and some compounds exhibited better effects than positive control ethaselen and 5-fluorouracil (5-FU) against various cancer cell lines. Furthermore, compounds 4b and 4m showed significant antitumor activities against SMMC-7721 cells with IC50 values of 1.89 and 1.89 μM, respectively. Compounds 4c and 4n displayed highly effective biological activities against MCF-7 cells with IC50 values of 2.88 and 2.28 μM, respectively. Compound 4i showed the best inhibitory effect against A549 cells with IC50 value of 1.76 μM.

Conclusion: The pharmacological results suggest that the substituent groups of phenyl ring on the 1,3,4-thiadiazole are vital for modulating antitumor activities against various cancer cell lines.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Azoles / pharmacology
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Fluorouracil / pharmacology
  • Humans
  • Isoindoles
  • Organoselenium Compounds / chemical synthesis
  • Organoselenium Compounds / chemistry
  • Organoselenium Compounds / pharmacology*
  • Structure-Activity Relationship
  • Thiadiazoles / chemical synthesis
  • Thiadiazoles / chemistry
  • Thiadiazoles / pharmacology*

Substances

  • Antineoplastic Agents
  • Azoles
  • Isoindoles
  • Organoselenium Compounds
  • Thiadiazoles
  • ebselen
  • Fluorouracil