Cytotoxic activities of amino acid-conjugate derivatives of abietane-type diterpenoids against human cancer cell lines

Chem Biodivers. 2013 Jul;10(7):1260-8. doi: 10.1002/cbdv.201300043.

Abstract

Nine amino acid conjugate derivatives, each 2-10 and 12-20, were prepared from abietic acid (1) and dehydroabietic acid (11), respectively, and they were evaluated for their cytotoxicities against four human cancer cell lines, i.e., leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK-BR-3). All compounds showed cytotoxicities against HL60 with IC50 values in the range of 2.3-37.3 μM. In addition, most of the derivatives exhibited moderate cytotoxicities against the other cancer cell lines. Among the derivatives, methyl N-[18-oxoabieta-8,11,13-trien-18-yl]-L-tyrosinate (19) exhibited potent cytotoxic activities against four cancer cell lines with IC50 values of 2.3 (HL60), 7.1 (A549), 3.9 (AZ521), and 8.1 μM (SK-BR-3). Furthermore, all derivatives were shown to possess high selective cytotoxic activities for leukemia cells, since they exhibited only weak cytotoxicities against normal lymphocyte cell line RPMI1788.

Keywords: Abietic acid; Amino acids; Cytotoxic activity; Dehydroabietic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abietanes / chemistry*
  • Abietanes / toxicity*
  • Amino Acids / chemistry*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / toxicity
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Screening Assays, Antitumor
  • HL-60 Cells
  • Humans

Substances

  • Abietanes
  • Amino Acids
  • Antineoplastic Agents