Harringtonine Ester Derivatives with Enhanced Antiproliferative Activities against HL-60 and HeLa Cells

Akihiro Ochi, Makoto Yoritate, Tomofumi Miyamoto, Kazuteru Usui, Gorawit Yusakul, Waraporn Putalun, Hiroyuki Tanaka, Go Hirai, Satoshi Morimoto, Seiichi Sakamoto

Research output: Contribution to journalReview articlepeer-review

2 Citations (Scopus)


Harringtonine (HT), produced from Cephalotaxus species, is known to exhibit potent antiproliferative activity against myeloid leukemia cells by inhibiting protein synthesis. A previous study using acute promyelocytic leukemia (HL-60) cells raised the possibility that the C-5′ methyl group of HT plays an important role in regulating leukemia cell line antiproliferative activity. In order to investigate the effect of hydrocarbon chains at C-5′ on the resultant activity, the C-5′ methyl group was replaced with various straight- and branched-chain hydrocarbons using the corresponding alcohols, and their antiproliferative activity against HL-60 and HeLa cells was investigated. As a result, 4′-n-heptyl-4′-demethylharringtonine (1f, n-heptyl derivative) showed the most potent cytotoxicity among the HT ester derivatives produced, with IC50values of 9.4 nM and 0.4 μM for HL-60 and HeLa cells, respectively. Interestingly, the cytotoxicity of derivative 1f against HL-60 and HeLa cells respectively was ∼5 (IC50= 50.5 nM) and ∼10 times (IC50= 4.0 μM) those of HT and ∼2 (IC50= 21.8 nM) and ∼4 times (IC50= 1.7 μM) more than homoharringtonine (HHT). These results demonstrate the potential of the derivative 1f as a lead compound against leukemia.

Original languageEnglish
Pages (from-to)345-351
Number of pages7
JournalJournal of Natural Products
Issue number2
Publication statusPublished - Feb 25 2022

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry


Dive into the research topics of 'Harringtonine Ester Derivatives with Enhanced Antiproliferative Activities against HL-60 and HeLa Cells'. Together they form a unique fingerprint.

Cite this