2,5-Disubstituted-1,3,4-oxadiazoles/thiadiazole as surface recognition moiety: design and synthesis of novel hydroxamic acid based histone deacetylase inhibitors

Bioorg Med Chem Lett. 2011 Oct 1;21(19):5735-8. doi: 10.1016/j.bmcl.2011.08.022. Epub 2011 Aug 8.

Abstract

The enzymatic inhibition of histone deacetylase activity has come out as a novel and effectual means for the treatment of cancer. Two novel series of 2-[5-(4-substitutedphenyl)-[1,3,4]-oxadiazol/thiadiazol-2-ylamino]-pyrimidine-5-carboxylic acid (tetrahydro-pyran-2-yloxy)-amides were designed and synthesized as novel hydroxamic acid based histone deacetylase inhibitors. The antiproliferative activities of the compounds were investigated in vitro using histone deacetylase inhibitory assay and MTT assay. The synthesized compounds were also tested for antitumor activity against Ehrlich ascites carcinoma cells in Swiss albino mice. The efforts were also made to establish structure-activity relationships among synthesized compounds. The results of the present studying indicates 2,5-disubstituted 1,3,4-oxadiazole/thiadiazole as promising surface recognition moiety for development of newer hydroxamic acid based histone deacetylase inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Carcinoma, Ehrlich Tumor / drug therapy
  • Cell Proliferation
  • Drug Design*
  • Drug Evaluation, Preclinical
  • Drug Screening Assays, Antitumor
  • Histone Deacetylase Inhibitors / chemical synthesis*
  • Histone Deacetylase Inhibitors / chemistry*
  • Histone Deacetylase Inhibitors / pharmacology
  • Hydroxamic Acids / chemistry
  • Mice
  • Neoplasms / drug therapy
  • Oxadiazoles / chemistry*
  • Structure-Activity Relationship
  • Surface Properties
  • Thiadiazoles / chemistry*
  • Zinc / chemistry

Substances

  • Antineoplastic Agents
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Oxadiazoles
  • Thiadiazoles
  • Zinc