A Novel Isoquinoline Derivative Anticancer Agent and Its Targeted Delivery to Tumor Cells Using Transferrin-Conjugated Liposomes

PLoS One. 2015 Aug 26;10(8):e0136649. doi: 10.1371/journal.pone.0136649. eCollection 2015.

Abstract

We have screened 11 isoquinoline derivatives and α-methylene-γ-butyrolactones using the 3-(4,5-dimethylthi-azol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay in HeLa and HEK-293T cells. Compound 2 was identified as potential anticancer agent. To further improve its therapeutic potential, this agent was incorporated into transferrin (Tf)-conjugated liposomes (LPs) for targeted delivery to tumor cells. We have demonstrated Tf-LP-Compound 2 have superior antitumor activity compared to non-targeted controls and the free drug. These data show Tf-LP-Compound 2 to be a promising agent that warrants further evaluation.

MeSH terms

  • Acrylates / administration & dosage*
  • Acrylates / chemistry
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / chemistry
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Drug Carriers*
  • Drug Screening Assays, Antitumor
  • Endocytosis
  • HEK293 Cells
  • HeLa Cells
  • Hep G2 Cells
  • Humans
  • Isoquinolines / administration & dosage*
  • Isoquinolines / chemistry
  • Lactones / chemistry
  • Lactones / pharmacology
  • Liposomes
  • Membrane Potential, Mitochondrial / drug effects
  • Quinolines / administration & dosage*
  • Quinolines / chemistry
  • Receptors, Transferrin / metabolism
  • Transferrin / chemistry*

Substances

  • Acrylates
  • Antineoplastic Agents
  • Drug Carriers
  • Isoquinolines
  • Lactones
  • Liposomes
  • Quinolines
  • Receptors, Transferrin
  • Transferrin

Grants and funding

The authors have no support or funding to report.