TY - JOUR
T1 - Sodium-Periodate-Mediated Harringtonine Derivatives and Their Antiproliferative Activity against HL-60 Acute Leukemia Cells
AU - Sakamoto, Seiichi
AU - Miyamoto, Tomofumi
AU - Usui, Kazuteru
AU - Tanaka, Hiroyuki
AU - Morimoto, Satoshi
N1 - Funding Information:
The research was funded by the Qdai-jump Research Program, Wakaba Challenge of Kyushu University. This work was also funded by a Grant-in-Aid for Young Scientists (B) of the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Number JP17K15466.
PY - 2018/1/26
Y1 - 2018/1/26
N2 - 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.
AB - 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.
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U2 - 10.1021/acs.jnatprod.7b00541
DO - 10.1021/acs.jnatprod.7b00541
M3 - Article
C2 - 29286665
AN - SCOPUS:85041205922
SN - 0163-3864
VL - 81
SP - 34
EP - 40
JO - Journal of Natural Products
JF - Journal of Natural Products
IS - 1
ER -