Current Topics in Medicinal Chemistry, Volume 3, No. 2, 2003
Contents
Natural
Products and Indigenous Medicine:Structure Elucidation and Therapeutic
Potential
Guest
Editor: Rachel Mata
Biodynamic Constituents
in the Mexican Morning Glories: Purgative Remedies Transcending Boundaries Pp. 111-131
Rogelio Pereda-Miranda and Moustapha Bah
Traditionally-Used
Antimalarials from the Meliaceae
Pp. 133-139
S. Omar, J. Zhang, S. MacKinnon, D. Leaman, T. Durst,
B.J.R. Philogene, J.T. Arnason, P.E. Sanchez-Vindas, L. Poveda, P.A. Tamez and
J.M. Pezzuto
Ethnobotany and
Natural Products: The Search for New Molecules, New Treatments of Old Diseases
or a Better Understanding of Indigenous Cultures? Pp. 141-154
Michael Heinrich
Plant-derived
Terpenoids and Analogues as Anti-HIV Agents Pp. 155-169
I-Chen Sun, Yoshiki Kashiwada, Susan L. Morris-Natschke
and Kuo-Hsiung Lee
Terpenoids:
Sources, Structure Elucidation and Therapeutic Potential in Inflammation Pp. 171-185
B. de las Heras, B. Rodríguez, L. Boscá and A.M. Villar
Hypericum
perforatum, a Source of Neuroactive Lead Structures Pp. 187-201
Luisella Verotta
Novel
Diarylheptanoids of Alpinia blepharocalyx Pp. 203-225
Shigetoshi Kadota, Yasuhiro Tezuka, Jeevan Kumar Prasain,
Mohammad Shawkat Ali and Arjun H. Banskota
Chemical
Constituents and Biological Activities of Vietnamese Medicinal Plants Pp. 227-248
Arjun H. Banskota, Yasuhiro Tezuka, Quan Le Tran and
Shigetoshi Kadota
[Back to top] Biodynamic
Constituents in the Mexican Morning Glories: Purgative Remedies Transcending
Boundaries
Rogelio Pereda-Miranda and Moustapha Bah
Jalap, a pre-Hispanic herbal remedy still considered a useful laxative,
is an ingredient in some over-the-counter products sold by herbalists in
contemporary Mexico. The purgative crude drugs are prepared from the roots of
several morning glories species which all have been identified as members of
the Ipomoea genus (Convolvulaceae). Their incorporation as therapeutical agents
into Europe is an outstanding example of the assimilation of botanical drugs
from the Americas as substitutes for traditional Old World remedies. Phytochemical
investigations on the resin glycosides, main constituents of these drugs, were
initiated during the second half of the XIX century; however, the structures of
their active ingredients had remained poorly known, and still are for some
members of these purgative root species. Modern analytical techniques with
higher resolution capabilities (HPLC) for the isolation of the active
principles of these crude drugs used in conjunction with powerful spectroscopic
methods (high field NMR) have facilitated the investigation of these relevant,
to the herbal product market, convolvulaceous species during the last decade.
The advantages and limitations of theses techniques will be discussed. This
review will also describe the ethnobotanical information associated with the
Mexican morning glory species and how the traditional usages of these plants
have played an important role in the selection of these materials for chemical
studies.
Little is as yet known about either the mechanism of purge action
caused by the resin glycosides or the ecological significance of these same
compounds for the producing plants. Over the five centuries of Mexican herbal
medicine, one hundred years of phytochemistry has only partially elucidated the
active ingredients of the jalap roots but has exemplified how to further
contemporary drug discoveries through the investigation of those plants
traditionally held to be economically and medicinally important in developing
countries.
[Back to top] Traditionally-Used
Antimalarials from the Meliaceae
S. Omar, J. Zhang, S. MacKinnon, D. Leaman, T. Durst,
B.J.R. Philogene, J.T. Arnason, P.E. Sanchez-Vindas, L. Poveda, P.A. Tamez and
J.M. Pezzuto
A quantitative ethnobotanical approach to antimalarial drug discovery
led to the identification of Lansium domesticum Corr. Ser. (Meliaceae) as an
important antimalarial used by Kenyah Dyak healers in Indonesian Borneo.
Triterpenoid lansiolides with antimalarial activity were isolated from the bark
and shown to have activity in both in vitro bioassays with Plasmodium
falciparum, and in mice infected with P. berghei. A survey of African and
tropical American Meliaceae led to further development of the limonoid gedunin
from the traditionally used medicinal plants, tropical cedar, Cedrela odorata
L., and neem, Azadirachta indica A. Juss. Gedunin has significant in vitro
activity but initially showed poor in vivo activity. In vivo activity was
improved by (1) incorporation into an easy to absorb suspension, (2)
preparation of a more stable compound, 7-methoxygedunin; and (3) synergism with
dillapiol, a cytochrome P450 3A4 inhibitor. The results show the potential for
both antimalarial drug and phytomedicine development from traditionally used
plants.
[Back to top] Ethnobotany
and Natural Products: The Search for New Molecules, New Treatments of Old
Diseases or a Better Understanding of Indigenous Cultures?
Michael Heinrich
Results of various projects on Mexican Indian ethnobotany and some of the
subsequent pharmacological and phytochemical studies are summarised focusing
both on chemical-pharmacological as well as anthropological
(ethnopharmacological) aspects of our research. We have identified taste and
smell properties of medicinal (vs. non-medicinal) plants as important
indigenous selection criteria. There exist welldefined criteria specific for
each culture, which lead to the selection of a plant as a medicine. This field
research has also formed a basis for studies on bioactive natural products from
selectedspecies. The bark of Guazuma ulmifolia showed antisecretory activity
(cholera toxin-induced chloride secretion in rabbit distal colon in an USSING
chamber). Active constituents are procyanidins with a polymerisation degree of
eight or higher. Byrsonima crassifolia yielded proanthocyanidins with (+)
epicatechin units and Baccharis conferta showed a dose-dependant antispasmodic
effect with the effect being particularly strong in flavonoid-rich fractions.
Our ethnopharmacological research led to the identification of sesquiterpene
lactones (SLs) like parthenolide as potent and relatively specific inhibitors
of the transcription factor NF-kB, an
important mediator of the inflammatory process. The inhibitory effect of SLs is
very strongly enhanced by the presence of such groups as the isoprenoid ring
system, a lactone ring containing a conjugated exomethylene group (a- methylene-g-lactone) and an a,b-unsaturated cyclopentenone or a conjugated
ester moieties. Our work also elucidated the NF-kB inhibiting
activity of the photosensitiser phaeophorbide A from Solanum diflorum
(Solanaceae) in PMA induced HeLa cells. Hyptis verticillata yielded a series of
lignans as well as sideritoflavone, rosmarinic acid and
(R)-5-hydroxypyrrolidin-2-one and is rich in essential oil (rich in b- pinene, â-pinene and thymol). Other species
investigated include Begonia heracleifolia, Crossopetalum gaumerii, Epaltes
mexicana, Pluchea symphytifolia and Xanthosoma robustum.
[Back to top] Plant-derived
Terpenoids and Analogues as Anti-HIV Agents
I-Chen Sun, Yoshiki Kashiwada, Susan L. Morris-Natschke
and Kuo-Hsiung Lee
The plant-derived terpenoids and analogues are reviewed with respect to
their anti-HIV activity, structure-activity relationships, and mechanism of
action. The active compounds include diterpenoid lactones, phenolic diterpenes,
atisane and kaurane diterpenes, phorbol diterpenes, triterpene glycosides,
friedelane triterpenes, taraxerane triterpenes, ursane triterpenes, lanostane
triterpene, lupane triterpenes, seco-ring A triterpenes, degraded triterpenes,
and cucurbitacin triterpenes. Positive new leads for drug development will be
highlighted.
[Back to top] Terpenoids:
Sources, Structure Elucidation and Therapeutic Potential in Inflammation
B. de las Heras, B. Rodríguez, L. Boscá and A.M.
Villar
Natural products research has lately undergone exponential growth owing
to advances in isolation techniques and in synthetic methods design, as well as
for the identification of a wide range of biological properties exhibited by
these compounds. In the present review, general remarks on the chemical
features, biosynthetic pathways, isolation and structure elucidation of
terpenoids are briefly discussed. In addition to this, recent work done on
anti-inflammatory terpenoids (diterpenoids, triterpenoids and sesquiterpene
lactones) with special emphasis on the last new molecular targets evaluated is
presented.
[Back to top] Hypericum
perforatum, a Source of Neuroactive Lead Structures
Luisella Verotta
Although St. John's wort has been known for thousands of years and has
been used for a variety of medicinal purposes, understanding of its activity
and mechanisms of action is relatively new and not well understood. While
researchers originally thought the naphthodianthrone hypericin was responsible
for Hypericum's antidepressant activity, it is now believed some other compound
or a combination of constituents exerts their antidepressant activity on the
body. Hypericum is unique in that it seems to impact all known
neurotransmitters at some level, directly, or indirectly through receptor
sensitivity and regulation. There has been a proliferation of clinical studies
on Hypericum in the last ten years, and even though some of these studies might
be methodologically flawed, the preponderance of the evidence proves Hypericum
to be beneficial for the treatment of mild-to-moderate depression, with a very
favorable side effect profile. One clinical trial carried out using two
extracts with different hyperforin content indicate this constituent as (one
of) the main active principle responsible for the antidepressant activity.
[Back to top] Novel
Diarylheptanoids of Alpinia blepharocalyx
Shigetoshi Kadota, Yasuhiro Tezuka, Jeevan Kumar Prasain, Mohammad Shawkat Ali and Arjun H. Banskota
The seeds of Alpinia blepharocalyx K. Schum.
(Zingiberaceae) is used in Chinese traditional medicine for the treatment of
stomach disorders. From the ether fraction of a 95% ethanolic extract, which
showed hepatoprotective and antiproliferative activities, we isolated 16 novel
diarylheptanoids bearing a chalcone or a flavanone moiety [calyxins A–H;
epicalyxins B–D, G, and H; 6-hydroxycalyxin F; and blepharocalyxins A and B]
together with seven known compounds, while the residual fraction of the
ethanolic extract gave 32 novel diarylheptanoids namely, calyxins A, E–G, and
I–M; epicalyxins B, F, I–K, and M; deoxycalyxin A; blepharocalyxins C–E;
neocalyxins A and B; (3S,5S)- and (3S,5R)-3-hydroxy-1-(4-
hydroxyphenyl)-5-methoxy-7-phenyl-6E-heptene, (3S,5S)- and
(3S,5R)-3-hydroxy-1-(4-hydroxyphenyl)-5- ethoxy-7-phenyl-6E-heptene,
(3S)-3-methoxy-1,7-bis(4-hydroxyphenyl)-6E-hepten-5-one, 1,7-bis(4-
hydroxyphenyl)-hepta-4E,6E-dien-3-one,
(3S,7R)-5,6-dehydro-1,7-bis(4-hydroxy-phenyl)-4''-de-O-methylcentrolobine,(3S,5S,6S,7R)-5,6-dihydroxy-1,7-bis(4
hydroxyphenyl)-4"-de-O-me-thylcentrolobine, (3S,5R,6S,7R)- and
(3S,5S,6R,7R)-5,6-dihydroxy-1,7-bis(4-hydroxyphenyl)-4"-de-O-methyl-centrolobine,
1,2- dihydro-bis(de-O-methyl)curcumin, and
(3S,7S)-5,6-dehydro-4''-de-O-methylcentrolobine, and one known diarylheptanoid
[(3S,5S)-3,5-dihydroxy-1,7-bis(4-hydroxyphenyl)heptane] together with 12 other
known phenolic compounds. Moreover, in vitro NO inhibitory and
antiproliferative activities of the isolated compounds were also tested and the
active constituents identified.
[Back to top] Chemical Constituents and Biological Activities
of Vietnamese Medicinal Plants
Arjun H. Banskota, Yasuhiro Tezuka, Quan Le Tran
and Shigetoshi Kadota
Every country has its own traditional medicine system originated from ancient times. Vietnam, a Southeast Asian country, has a unique traditional medicine system. Several medicinal plants are still used by different ethnic societies of Vietnam for treating several diseases due to their easy availability. Combretum quadrangulare, Panax vietnamensis (Vietnamese Ginseng), Dracaena angustifolia (Nam Ginseng) and Orthosiphon stamineus are among the popular medicinal plants used in Vietnamese traditional medicine for curing various diseases and to improve physical strength. In this review article, we discuss the chemical analysis as well as biological activities of these Vietnamese medicinal plants in order to establish the relation between their therapeutic uses and scientific findings..