Apoptosis induced by synthetic compounds containing a 3,4,5-trimethoxyphenyl fragment against lymphoid immature neoplasms

Biochem Cell Biol. 2019 Oct;97(5):630-637. doi: 10.1139/bcb-2018-0316. Epub 2019 Mar 8.

Abstract

T-cell acute lymphoblastic leukemia is an aggressive hematological malignancy originating from the malignant transformation of progenitor T cells at different stages of development. The treatment causes severe adverse effects and is associated with relapses and high morbidity and mortality rates. The present study aimed to evaluate the cytotoxic activity of 28 new compounds containing 3,4,5-trimethoxyphenyl analogues on hematological neoplastic cells lines. Cytotoxicity screening by the MTT method revealed that compound 1d was the most promising. Cell viability of neoplastic cells decreased in a concentration- and time-dependent manner, with compound 1d not causing hemolysis or reducing peripheral blood mononuclear cells viability, suggesting a selective cytotoxicity. We also suggested that compound 1d induced apoptotic-like cell death with mitochondrial involvement in Jurkat cells.

Keywords: 3,4,5-trimethoxyphenyl analogues; acute leukemia; analogues de 3,4,5-triméthoxyphényle; apoptose; apoptosis; cytotoxicity; cytotoxicité; leucémie aigüe.

MeSH terms

  • Acetophenones / chemical synthesis
  • Acetophenones / chemistry
  • Acetophenones / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Hydrazones / chemical synthesis
  • Hydrazones / chemistry
  • Hydrazones / pharmacology*
  • Leukemia, Lymphoid / drug therapy*
  • Leukemia, Lymphoid / pathology
  • Molecular Structure
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Acetophenones
  • Antineoplastic Agents
  • Hydrazones