Drugs from the Cloud Forest
The Search for New
Medicines from Monteverde, Costa Rica
The purpose of this research
is to carry out exploratory research on the isolation, biological testing and
identification of potentially useful natural products. In collaboration with William A. Haber of the Missouri
Botanical Garden, we have investigated plant materials from Monteverde, Costa Rica. Specifically, we collect plant materials from the
Monteverde Cloud Forest Reserve and the Monteverde community, Costa Rica. We
concentrate our screening on the Araliaceae, Euphorbiaceae, Myrtaceae,
Clusiaceae, and Rutaceae families. Crude extracts from these plants are tested
for fungicidal and antibacterial activity, antiviral activity, and
cytotoxicity. Those extracts that show biological activity are fractionated and
the active compounds identified.
This project is especially attractive in
that not only does it provide us with additional new pharmacopeia from natural
sources (before those sources are lost through deforestation and other habitat
destruction), but it also serves to provide additional arguments for conserving
the diversity of the tropics as well as identifying potential alternative (and
ecologically less damaging) “cash crops” for critical tropical habitats. Thus,
this project also addresses the problem of the degenerating environment in
tropical America; the crisis of the decline of biodiversity in these areas.
Specifically, this project involves:
a)an
inventory of tropical biota in terms of medicinal natural products;
b)conservation
of tropical natural areas; and
c)providing
alternative cash crops for critical tropical habitats.
Another attractive feature of this
project is the interdisciplinary nature of the research. There are three
principal collaborators who bring many different areas of complementary
expertise into the project. In addition, the project provides hands-on
experience for undergraduate students. The Departments of Chemistry and
Biological Sciences and the University of Alabama in Huntsville are all acutely
aware of the potential shortage of future scientists and we are therefore
committee to undergraduate research participation as part of quality scientific
education and training.
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Some
Representative Publications:
Setzer, W.N., M.N. Flair, K.G. Byler,
J. Huang, M.A. Thompson, A.F. Setzer, D.M. Moriarity, R.O. Lawton, and D.B.
Windham-Carswell. 1992. Antimicrobial and cytotoxic activity of crude extracts
of Araliaceae from Monteverde, Costa Rica. Brenesia 38: 123-130.
Tropical plant materials from the ginseng
family (Araliaceae) have been collected from the Monteverde Cloud Forest
Reserve, Costa Rica, and the Monteverde community. These plants were extracted
(chloroform extraction and ethanol extraction) and the crude extracts tested
for fungidical, bacteriocidal, and cytotoxic activity. None of the crude
extracts showed antibacterial activity. Chloroform extracts from various Oreopanax
spp. did show antifungal activity, however. Crude ethanol extracts were
screened for potential antitumor activity in vitro against a human
hepatocellular carcinoma cell line (Hep G2). Six members of Araliaceae show
remarkable in-vitro cytotoxic activity against human Hep G2
hepatocellular carcinoma cells but limited cytotoxic activity against normal
adult rat hepatocytes.
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Dendropanax gonatopodus |
The crude ethanol extract from the leaves
of Tovomitopsis psychotriifolia (Clusiaceae) exhibits antibacterial
activity against Bacillus cereus, Staphylococcus aureus, and Pseudomonas
aeruginosa. The biological active agent in the extract has been isolated by
chromatographic techniques and identified by NMR spectroscopy as trans-d-tocotrienoloic
acid.
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trans-d-tocotrienoloic acid |
The crude ethanol extract from the leaves
of Dendropanax arboreus (Araliaceae) from Monteverde, Costa Rica,
exhibits cytotoxic activity against Hep-G2, A-431, H-4IIE, and L-1210 tumor
cell lines, but is not toxic against normal hepatocytes. The active component
has been isolated by activity-directed separation and identification by 1H-
and 13C-NMR spectroscopy as the acetylenic compound cis-1,9,16-heptadecatriene-4,6-diyne-3,8-diol.
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Dendropanax arboreus |
cis-1,9,16-heptadecatriene-4,6-diyne-3,8-diol |
Moriarity, D.M., J. Huang, C.A. Yancey,
P. Zhang, W.N. Setzer, R.O. Lawton, R.B. Bates, and S. Caldera. 1998. Lupeol is
the cytotoxic principle in the leaf extract of Dendropanax cf. querceti. Planta
Medica 64: 370-372.
The crude ethanol extract from the leaves
of Dendropanax cf. querceti (Araliaceae) from Monteverde, Costa
Rica, exhibits cytotoxic activity against Hep-G2, A-431, and H-4IIE tumor cell
lines. The active component has been isolated by activity-directed separation
and identified by 1H- and 13C-NMR spectroscopy as the
triterpene lupeol. The mechanism of cytotoxic activity of lupeol has been
determined to be inhibition of topoisomerase II.
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Lupeol |
Setzer, W.N., M.C. Setzer, A.L.
Hopper, D.M. Moriarity, G.K. Lehrman, K.L. Niekamp, S.M. Morcomb, R.B. Bates,
K.J. McClure, C.C. Stessman, and W.A. Haber. 1998. The cytotoxic activity of a Salacia
liana species from Monteverde, Costa Rica, is due to a high concentration of
tingenone. Planta Medica 64: 583.
The crude chloroform bark extract from an
undescribed Salacia liana species shows in-vitro cytotoxic
activity against Hep-G2, H-4IIE, and SK-Mel-28 tumor cells. Flash
chromatography led to isolation of the following compounds: friedelin,
1-hydroxy-3,6-dimethoxy-8-methyl-9H-xanthen-9-one, friedelan-3-on-29-al,
canophyllol, 29-hydroxyfriedelan-3-one, and the cytotoxic component, tingenone
(representing 0.24% of the fresh bark).
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Tingenone |
The leaf essential oil of an undescribed
species of Myrcianthes has been obtained from Monteverde, Costa Rica.The
essential oil exhibits in-vitro cytotoxic activity against Hep-G2 and
SK-Mel-28 human tumor cell lines.A GC/MS analysis shows the essential oil to be
composed of 2-heptanol, a-pinene,b-pinene, limonene, cineole, and a-terpineol.a-Pinene, b-pinene, and limonene
account for the cytotoxic acivity of the leaf essential oil of Myrcianthes
sp. nov. “black fruit”.
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Myrcianthes “black fruit” |
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a-Pinene |
b-Pinene |
Limonene |
1,8-Cineol |
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A phytochemical investigation of the
chloroform leaf extract of Alchornea latifolia (Euphorbiaceae) from
Monteverde, Costa Rica, has been undertaken. Along with the triterpenoids
taraxerone, friedelin, epifriedelinol, and taraxerol, the plant also
contains seco-3,4-friedelin (dihydroputranjivic acid) and
seco-3,4-taraxerone. These A-ring-opened triterpenoids show in-vitro
cytotoxic activity against Hep-G2 and A-431 human cancer cell lines and are
potent inhibitors of topoisomerase II.
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seco-3,4-Friedelin |
The crude bark extract of Stauranthus
perforatus showed in-vitro cytotoxic activity against Hep-G2 (human
hepatocellular carcinoma) and MDA-MB-231 (human mammary adenocarcinoma)
cells.The cytotoxic compounds proved to be the quinoline alkaloids skimmianine
and veprisine, and the furocoumarin heraclenin.
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Skimmianine |
Veprisine |
Heraclenin |
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The
crude dichloromethane bark extract of Salacia petenensis
(Hippocrateaceae) from Monteverde, Costa Rica, shows antibacterial and
cytotoxic activity.Bioactivity-directed separation led to the isolation of
tingenone and netzahualcoyonol as the biologically active materials.Also
isolated from the extract were 3-methoxyfriedel-2-en-1-one (a new natural
product) and 29-hydroxyfriedelan-3-one.The structures of these compounds were
elucidated on the basis of NMR spectral analysis. Molecular orbital
calculations have been carried out using the semi-empirical PM3 and Hartee-Fock
3-21G ab initio techniques on the quinone-methide nortriterpenoids
tingenone and netzahualcoyonol, as well as on the nucleotide bases adenine,
guanine, cytosine, and thymine.The molecular orbital calculations suggest that
a possible mode of cytotoxic action of quinone-methide triterpenoids involves
quasi-intercalative interaction of the compounds with DNA followed by
nucleophilic addition of the DNA base to carbon-6 of the triterpenoid.
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Netzahualcoyonol |
Costa Rical Floral Biodiversity
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UAH Natural Products Group Page
August, 2000