title: 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.affiliation: Program for Collaborative Research in the Pharmaceutical Sciences and Department of Medicinal Chemistry, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
authors.forename: Jian-Qiao
authors.initials: JQ
authors.lastname: Gu
authors.forename: Joell J
authors.initials: JJ
authors.lastname: Gills
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Park
authors.forename: Eugenia
authors.initials: E
authors.lastname: Mata-Greenwood
authors.forename: Michael E
authors.initials: ME
authors.lastname: Hawthorne
authors.forename: Franklin
authors.initials: F
authors.lastname: Axelrod
authors.forename: Pedro I
authors.initials: PI
authors.lastname: Chavez
authors.forename: Harry H S
authors.initials: HH
authors.lastname: Fong
authors.forename: Rajendra G
authors.initials: RG
authors.lastname: Mehta
authors.forename: John M
authors.initials: JM
authors.lastname: Pezzuto
authors.forename: A Douglas
authors.initials: AD
authors.lastname: Kinghorn
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D019659:Asteraceae / Q000737:chemistry*; D001551:Benz(a)Anthracenes / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D007951:Leukemia, Myeloid; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced; D051379:Mice; D008807:Mice, Inbred BALB C; D008968:Molecular Conformation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010946:Plants, Medicinal / Q000737:chemistry*; D011647:Puerto Rico; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
chemical_list: C457141:2-hydroxytirotundin; C457143:3-acetoxydiversifolol; D000972:Antineoplastic Agents, Phytogenic; D001551:Benz(a)Anthracenes; D007783:Lactones; D012717:Sesquiterpenes; C457142:tithofolinolide; C046810:7,12-dihydroxymethylbenz(a)anthracene