Arylboronate prodrugs of doxorubicin as promising chemotherapy for pancreatic cancer

Bioorg Chem. 2019 Oct:91:103158. doi: 10.1016/j.bioorg.2019.103158. Epub 2019 Jul 24.

Abstract

This study describes the synthesis of arylboronate-based ROS-responsive prodrugs of doxorubicin and their biological evaluation as anticancer agents. The determination of the most sensitive cancer type toward arylboronate prodrugs is crucial for further consideration of these molecules in clinical phase. To address this goal, an arylboronate-based profluorescent probe was used to compare the capacity of various cancer cell lines to efficiently convert the precursor into the free fluorophore. On the selected MiaPaCa-2 pancreatic cancer cells, a benzeneboronate prodrug exhibited 67% of the cytotoxicity obtained with the free doxorubicin. The prodrug was also able to induce tumor regression on MiaPaCa-2 pancreatic tumor model in ovo. Using this model, the amount of free doxorubicin liberated from this prodrug into the tumor was equivalent to the quantity measured after direct intratumoral injection of the same concentration of doxorubicin.

Keywords: Anticancer chemotherapy; Doxorubicin; Prodrug; Reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / pharmacology
  • Boronic Acids / chemistry*
  • Chick Embryo
  • Chorioallantoic Membrane
  • Doxorubicin / pharmacology*
  • Drug Delivery Systems
  • Drug Synergism*
  • Heterocyclic Compounds / chemistry*
  • Humans
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology
  • Prodrugs / chemistry*
  • Prodrugs / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Antibiotics, Antineoplastic
  • Boronic Acids
  • Heterocyclic Compounds
  • Prodrugs
  • Doxorubicin