Sesquiterpenoids from Tithonia diversifolia with potential cancer chemopreventive activity.

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, 2alpha-hydroxytirotundin (1), tithofolinolide (2), and 3alpha-acetoxydiversifolol (3), along with eight known sesquiterpene lactones, 3beta-acetoxy-8beta-isobutyryloxyreynosin (4), tagitinin C (5), 1beta,2alpha-epoxytagitinin C (6), 4alpha,10alpha-dihydroxy-3-oxo-8beta-isobutyryloxyguaia-11(13)-en-12,6alpha-olide (7), 3alpha-acetoxy-4alpha-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 microg/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.

• Authors: 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
• Journal: Journal of natural products (J Nat Prod) Vol. 65 Issue 4 Pg. 532-6 (Apr 2002) ISSN: 0163-3864 [Print] United States
• PMID: 11975495 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 2-hydroxytirotundin
• 3-acetoxydiversifolol
• Antineoplastic Agents, Phytogenic
• Benz(a)Anthracenes
• Lactones
• Sesquiterpenes
• tithofolinolide
• 7,12-dihydroxymethylbenz(a)anthracene

Topics

• Animals
• Antineoplastic Agents, Phytogenic (chemistry, isolation & purification, pharmacology)
• Asteraceae (chemistry)
• Benz(a)Anthracenes (pharmacology)
• Chromatography, High Pressure Liquid
• Humans
• Lactones (chemistry, isolation & purification, pharmacology)
• Leukemia, Myeloid
• Mammary Neoplasms, Experimental (chemically induced)
• Mice
• Mice, Inbred BALB C
• Molecular Conformation
• Molecular Structure
• Nuclear Magnetic Resonance, Biomolecular
• Plants, Medicinal (chemistry)
• Puerto Rico
• Sesquiterpenes (chemistry, isolation & purification, pharmacology)