N-(2-Hydroxypropyl)methacrylamide Copolymer-Drug Conjugates for Combination Chemotherapy of Acute Myeloid Leukemia

Macromol Biosci. 2016 Jan;16(1):121-8. doi: 10.1002/mabi.201500193. Epub 2015 Jul 29.

Abstract

There is a need for new treatment strategies of acute myeloid leukemia (AML). In this study, four different drugs, including cytarabine, daunorubicin, GDC-0980, and JS-K, were investigated in vitro for the two-drug combinations treatment of AML. The results revealed that cytarabine and GDC-0980 had the strongest synergism. In addition, cell cycle analysis was conducted to investigate the effect of the different combinations on cell division. For future in vivo application, N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-cytarabine and GDC-0980 conjugates were synthesized, respectively. In vitro studies demonstrated that both conjugates had potent cytotoxicity and their combination also showed strong synergy, suggesting a potential chemotherapeutic strategy for future AML treatment.

Keywords: N-(2-hydroxypropyl)methacrylamide; acute myeloid leukemia; combination chemotherapy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acrylamides*
  • Bridged Bicyclo Compounds, Heterocyclic / therapeutic use
  • Cell Cycle / drug effects
  • Cytarabine / therapeutic use
  • Daunorubicin / therapeutic use
  • Drug Carriers / chemistry
  • Drug Carriers / therapeutic use*
  • Drug Synergism
  • Drug Therapy, Combination
  • Female
  • HL-60 Cells
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Pyrimidines / therapeutic use

Substances

  • 1-(4-((2-(2-aminopyrimidin-5-yl)-7-methyl-4-morpholinothieno(3,2-d)pyrimidin-6-yl)methyl)piperazin-1-yl)-2-hydroxypropan-1-one
  • Acrylamides
  • Bridged Bicyclo Compounds, Heterocyclic
  • Drug Carriers
  • Pyrimidines
  • Cytarabine
  • N-(2-hydroxypropyl)methacrylamide
  • Daunorubicin