Gu Jian-Qiao, Gills Joell J, Park Eun Jung, Mata-Greenwood Eugenia, Hawthorne Michael E, Axelrod Franklin, Chavez Pedro I, Fong Harry H S, Mehta Rajendra G, Pezzuto John M, Kinghorn A Douglas
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.
J Nat Prod. 2002 Apr;65(4):532-6. doi: 10.1021/np010545m.
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.
使用人结肠癌细胞（Col2）进行抗增殖生物测定，对肿柄菊地上部分的乙酸乙酯提取物进行活性导向分馏，从而分离出三种新的倍半萜类化合物，2α-羟基tirotundin（1）、肿柄菊醇内酯（2）和3α-乙酰氧基肿柄菊醇（3），以及八种已知的倍半萜内酯，3β-乙酰氧基-8β-异丁酰氧基reynosin（4）、tagitinin C（5）、1β,2α-环氧tagitinin C（6）、4α,10α-二羟基-3-氧代-8β-异丁酰氧基愈创木-11(13)-烯-12,6α-内酯（7）、3α-乙酰氧基-4α-羟基-11(13)-桉叶-12-酸甲酯、17,20-二羟基香叶基 nerol、tagitinin A和tirotundin。通过测量Col2细胞中的抗增殖活性以及人早幼粒细胞白血病（HL-60）细胞中的细胞分化诱导情况，对这些分离物作为癌症化学预防剂的潜力进行了评估。然后在小鼠乳腺器官培养试验中研究了选定化合物抑制7,12-二甲基苯并[a]蒽诱导的癌前病变的能力。在这些分离物中，5和6表现出显著的抗增殖活性，2、4和7诱导HL-60细胞分化，并且4在小鼠乳腺器官培养试验中显著抑制（10μg/mL时为63.0%）病变形成。通过光谱分析阐明了1-3的化学结构。1和2的绝对构型通过Mosher酯法确定。
