Sesquiterpenoids from Tithonia diversifolia with potential cancer chemopreventive activity

Jian Qiao Gu, Joell J. Gills, Eun Jung Park, Eugenia Mata-Greenwood, Michael E. Hawthorne, Franklin Axelrod, Pedro I. Chavez, Harry H.S. Fong, Rajendra G. Mehta, John M. Pezzuto, A. Douglas Kinghorn

Research output: Contribution to journalArticlepeer-review

Abstract

Activity-guided fractionation of an ethyl acetate extract of the aerial parts of Tithonia diversifolia, using an antiproliferation bioassay performed with human colon cancer (Col2) cells, led to the isolation of three new sesquiterpenoids, 2α-hydroxytirotundin (1), tithofolinolide (2), and 3α-acetoxydiversifolol (3), along with eight known sesquiterpene lactones, 3β-acetoxy-8β-isobutyryloxyreynosin (4), tagitinin C (5), 1β,2α-epoxytagitinin C (6), 4α,10α-dihydroxy-3-oxo-8β-isobutyryloxyguaia-11(13) -en-12,6α-olide (7), 3α-acetoxy-4α-hydroxy-11(13)-eudesmen-12-oic acid methyl ester, 17,20-dihydroxygeranylnerol, tagitinin A, and tirotundin. These isolates were evaluated for their potential as cancer chemopreventive agents, by measuring antiproliferative activity in Col2 cells and induction of cellular differentiation in human promyelocytic leukemia (HL-60) cells. Selected compounds were then investigated for their ability to inhibit 7,12-dimethylbenz[a]anthracene-induced preneoplastic lesions in a mouse mammary organ culture assay. Among these isolates, 5 and 6 showed significant antiproliferative activity, 2, 4, and 7 induced HL-60 cellular differentiation, and 4 significantly inhibited (63.0% at 10 μg/mL) lesion formation in the mouse mammary organ culture assay. The chemical structures of 1-3 were elucidated by spectroscopic analysis. The absolute configurations of 1 and 2 were determined by Mosher ester methodology.

Original languageEnglish (US)
Pages (from-to)532-536
Number of pages5
JournalJournal of Natural Products
Volume65
Issue number4
DOIs
StatePublished - 2002
Externally publishedYes

ASJC Scopus subject areas

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

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