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Bioactivity‐guided Isolation of Antiproliferative Diterpenoids from Euphorbia kansui
Author(s) -
Wang HongYing,
Wang JunSong,
Wei DanDan,
Wang XiaoBing,
Luo Jun,
Yang MingHua,
Kong LingYi
Publication year - 2012
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.3640
Subject(s) - stereochemistry , diterpene , euphorbiaceae , euphorbia , terpenoid , dichloromethane , epimer , chemistry , in vitro , solvent , biology , organic chemistry , biochemistry , botany
Cytotoxic assay guided multistep separation on the dichloromethane extract of the roots of Euphorbia kansui resulted in the isolation of 10 ingenol‐type diterpenoids (1–4 and 7–12), of which, 5‐ O ‐(2′ E ,4′ E ‐decadienoyl)‐20‐ O ‐acetylingenol (1) is a new compound, and two are jatrophane‐type diterpenoids (13–14). Interconversion of two pairs of positional ester isomers (1–4) in aqueous alcoholic solution was observed, the transesterification mechanism of which was speculated and confirmed by acylation of 3 and 4 to 6 and 5, respectively. All the isolates and the two acyl derivatives (5 and 6) were evaluated in vitro for their cytotoxicities in Bel‐7402, Bel‐7402/5FU, BGC‐823 and SGC‐7901 cell lines. The 12 ingenol‐type diterpenoids exhibited weak to moderate cytotoxicities, whereas the two jatrophane‐type diterpenoids displayed no antiproliferative effects, which, however, may increase the antitumour efficacy of those ingenol‐type diterpenoids. The structure‐–activity relationships were investigated by principal component analysis (PCA) of the pIC 50 (−logIC 50 ) values of the compounds tested and their calculated molecular descriptors. The pIC 50 values were highly correlated with most descriptors, especially the highest occupied molecular orbital energy ( E HOMO ), absolute hardness (η) and positively charged solvent accessible surface areas (P‐ASA). As the values of E HOMO increase, η and P‐ASA decrease, and the antiproliferative effects of these compounds increase. Copyright © 2011 John Wiley & Sons, Ltd.