Synthesis and in vitro antitumor effect of diclofenac and fenoprofen thiolated and nonthiolated polyaspartamide-drug conjugates

Eur J Med Chem. 2007 Jan;42(1):20-9. doi: 10.1016/j.ejmech.2006.08.009. Epub 2006 Sep 27.

Abstract

This paper reports the synthesis and antiproliferative effects of new thiomer-diclofenac and fenoprofen conjugates, hydrophilic, bioadhesive, polymeric prodrugs, as well as antiproliferative effects of diclofenac, fenoprofen and a series of previously described polymer-fenoprofen conjugates on five tumor cell lines. Thiolated and nonthiolated polyaspartamides were the chosen polymeric components. Drug-loading ranged from 5.6 to 22.4%, and the amount of SH groups ranged from 6.9 to 45.6micromol g(-1). Tensile studies demonstrated a clear correlation between the amount of thiol and the mucoadhesive properties of the conjugates. The growth-inhibitory activity of the tested polymer-drug conjugates demonstrates that polyaspartamide-type polymers, especially thiolated polymers, enable inhibition of tumor cell growth with significantly lower doses of the active substance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / chemistry
  • Cell Line, Tumor
  • Diclofenac / analogs & derivatives*
  • Diclofenac / chemical synthesis*
  • Diclofenac / pharmacology
  • Drug Carriers
  • Drug Screening Assays, Antitumor
  • Fenoprofen / analogs & derivatives*
  • Fenoprofen / chemical synthesis*
  • Fenoprofen / pharmacology
  • Humans
  • Nylons / chemistry*
  • Prodrugs / chemical synthesis*
  • Prodrugs / pharmacology
  • Structure-Activity Relationship
  • Sulfhydryl Compounds / chemistry*

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Nylons
  • Prodrugs
  • Sulfhydryl Compounds
  • Diclofenac
  • Aspartic Acid
  • Fenoprofen