Fatty acyl amide derivatives of doxorubicin: Synthesis and in vitro anticancer activities

Bhupender S. Chhikara, Nicole St. Jean, Deendayal Mandal, Anil Kumar, Keykavous Parang

Research output: Contribution to journalArticle

Abstract

Doxorubicin is extensively used in anticancer therapy. Doxorubicin is highly hydrophilic, has short half-life, and its use is associated with severe side effects at high doses. Fatty acyl amide derivatives of doxorubicin were synthesized with the expectation to improve the lipophilicity and anticancer activity of the drug. The lipophilicity was enhanced with the increase in chain length of fatty acyl moiety. Conjugation of 4′-amino group with fatty acids through an amide bond reduced the anticancer activity in leukemia, breast, ovarian, and colon cancer cell lines, suggesting that the presence of free amino group is required for anticancer activity of doxorubicin. Dodecanoyl-doxorubicin derivative was consistently the most effective among the synthesized derivatives and inhibited the proliferation of colon (HT-29) and ovarian (SK-OV-3) cancer cells by 64% and 58%, respectively, at a concentration of 1 μM after 96 h incubation.

Original languageEnglish (US)
Pages (from-to)2037-2042
Number of pages6
JournalEuropean Journal of Medicinal Chemistry
Volume46
Issue number6
DOIs
StatePublished - Jun 2011
Externally publishedYes

Keywords

  • Anticancer
  • Doxorubicin
  • Fatty acids
  • Lipophilicity
  • Prodrug
  • Sustained delivery

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

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