Antileishmanial and cytotoxic activity of some highly oxidized abietane diterpenoids from the bald cypress, Taxodium distichum

TitleAntileishmanial and cytotoxic activity of some highly oxidized abietane diterpenoids from the bald cypress, Taxodium distichum
Publication TypeJournal Article
Year of Publication2016
AuthorsNaman C.B, Gromovsky A.D, Vela C.M, Fletcher J.N, Gupta G., Varikuti S., Zhu X.H, Zywot E.M, Chai H., Werbovetz K.A, Satoskar A.R, Kinghorn A.D
JournalJournal of Natural Products
Volume79
Pagination598-606
Date Published2016/03
Type of ArticleArticle
ISBN Number0163-3864
Accession NumberWOS:000373031200020
Keywordsconstituents; ferruginol; identification; leishmania-donovani; methide tumor inhibitors; microstegiol; quinones; roots; taxodone
Abstract

Two new compounds, namely, a para-benzoquinone ring-containing abietane (1) and a para-benzoquinone ring containing 7,8-seco-abietane (2), and 14 other known highly oxidized abietane diterpenoids (3-16) were isolated from an extract prepared from the cones of Taxodium distichum, collected in central Ohio. The active subfraction from which all compounds isolated in this study were purified was tested in vivo using Leishmania donovani-infected mice and was found to dose dependently reduce the parasite burden in the murine livers after iv administration of this crude mixture at 5.6 and 11.1 mg/kg. The structures of 1 and 2 were established by detailed 1D- and 2D-NMR experiments, HRESIMS data, and electronic circular dichroism studies. Compounds 3 and 4 were each fully characterized spectroscopically and also isolated from a natural source for the first time. Compounds 2-16 were tested in vitro against L. donovani promastigotes and L. amazonensis intracellular amastigotes. Compound 2 was the most active against L. amazonensis amastigotes (IC50 = 1.4 mu M), and 10 was the most potent against L. donovani promastigotes (IC50 = 1.6 mu M). These compounds may be suggested for further studies such as in vivo experimentation either alone or in combination with other Taxodium isolates.

DOI10.1021/acs.jnatprod.5b01131
Short TitleJ. Nat. Prod.
Student Publication: 
No
Research Topics: 
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