Synthesis and characterization of a photoresponsive doxorubicin/combretastatin A4 hybrid prodrug

Bioorg Med Chem Lett. 2019 Feb 1;29(3):487-490. doi: 10.1016/j.bmcl.2018.12.017. Epub 2018 Dec 10.

Abstract

To explore the application of photoremovable protecting groups (PPGs) in the field of combination chemotherapy, we designed and synthesized a photoresponsive hybrid prodrug 4 that bearing both doxorubicin (DOX) and combretastatin A4 (CA4). Light triggered drug release investigation found that DOX release was mainly accomplished by 405 nm light while CA4 release was mainly triggered by 365 nm light, i.e., prodrug 4 exhibited a quasi-sequential release behavior when a sequential light irradiation strategy was applied. Cell viability evaluation confirmed the increased cytotoxicity of prodrug 4 compared with individual drugs towards MDA-MB-231cells, indicating that a synergistic effect was achieved.

Keywords: Combination chemotherapy; Combretastatin; Doxorubicin; Hybrid prodrug; Photoresponsive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology*
  • Drug Liberation
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Photosensitizing Agents / chemical synthesis
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology*
  • Prodrugs / chemical synthesis
  • Prodrugs / chemistry
  • Prodrugs / pharmacology*
  • Stilbenes / chemistry
  • Stilbenes / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Photosensitizing Agents
  • Prodrugs
  • Stilbenes
  • Doxorubicin
  • fosbretabulin