Harringtonine (HT) is a naturally occurring alkaloid isolated from the plant genus Cephalotaxus. It possesses antileukemic activity and has been clinically utilized for the treatment of acute leukemia and lymphoma. Sodium periodate (NaIO 4 ) was reacted with HT to produce five HT derivatives including four novel compounds. Their antiproliferative activity against HL-60 acute promyelocytic leukemia cells revealed that the presence of the C-5′ methyl group enhances the antiproliferative activity because the IC 50 values of the HT derivatives, including HT1 (5′-de-O-methylharringtonine), were at least 2000 times higher (>100 μM) than that of HT (∼47 nM). In addition, an indirect competitive enzyme-linked immunosorbent assay (icELISA) using a monoclonal antibody against HT (mAb 1D2) revealed that these antiproliferative activities were related to their cellular uptake. These results indicated that esterification of HT1 at the C-4′ carboxylic acid group may enhance the antiproliferative activity of HT.
All Science Journal Classification (ASJC) codes
- Analytical Chemistry
- Molecular Medicine
- Pharmaceutical Science
- Drug Discovery
- Complementary and alternative medicine
- Organic Chemistry