Regioselective synthesis and biological studies of novel 1-aryl-3, 5-bis (het) aryl pyrazole derivatives as potential antiproliferative agents

Mol Cell Biochem. 2017 Feb;426(1-2):149-160. doi: 10.1007/s11010-016-2887-7. Epub 2016 Nov 24.

Abstract

Pyrazole moiety represents an important category of heterocyclic compound in pharmaceutical and medicinal chemistry. The novel 1-aryl-3, 5-bis (het) aryl pyrazole derivatives were synthesized with complementary regioselectivity. The chemical structures were confirmed by IR, 1H NMR, 13C NMR, and mass spectral analysis. The chemical entities were screened in various cancer cell lines to assess their cell viability activity. Results showed that the compound 3-(1-(4-bromophenyl)-5-phenyl-1H-pyrazol-3-yl) pyridine (5d) possessed maximum cytotoxic effect against breast cancer and leukemic cells. The cytotoxicity was confirmed by live-dead cell assay and cell cycle analysis. Mitochondrial membrane potential, Annexin V-FITC staining, DNA fragmentation, Hoechst staining, and western blot assays revealed the ability of compound 5d to induce cell death by activating apoptosis in cancer cells. Thus, the present study demonstrates that compound 5d could be an attractive chemical entity for the development of small molecule inhibitors for treatment of leukemia and breast cancer.

Keywords: Apoptosis; Breast cancer; Dithioesters; MCF7; Pyrazole; Regioselectivity.

MeSH terms

  • Animals
  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Cell Death / drug effects
  • Cell Proliferation / drug effects*
  • Cytotoxins* / chemical synthesis
  • Cytotoxins* / chemistry
  • Cytotoxins* / pharmacology
  • Female
  • Humans
  • K562 Cells
  • Leukemia / drug therapy*
  • Leukemia / metabolism
  • MCF-7 Cells
  • Mass Spectrometry
  • Mice
  • Pyrazoles* / chemical synthesis
  • Pyrazoles* / chemistry
  • Pyrazoles* / pharmacology

Substances

  • Antineoplastic Agents
  • Cytotoxins
  • Pyrazoles