Current Organic Chemistry, Volume 7, No. 12, 2003
Contents
Natural Products Chemistry
Guest Editor: K. Hostettmann
Plant Constituents with Hormonal Effects Pp.1151-1161
Christian
Terreaux, Johanne Polasek and Kurt Hostettmann
Plant Substances as Antiviral Agents: An Update
(1997-2001) Pp.1163-1180
P.
Cos , D. Vanden Berghe , T. De Bruyne , A.J. Vlietinck
Brominated Diterpenes of Marine Origin Pp.1181-1229
J.-M.
Kornprobst and H.-S. Al-Easa
Recent Developments with 1,2,4-Trioxane-Type Artemisinin
Analogues Pp.1231-1255
G.
Bez, B. Kalita, P. Sarmah, N.C. Barua
and D.K. Dutta
Approaches Towards the Synthesis of Cephalostatins,
Ritterazines and Saponins from Ornithogalum saundersiae – New Natural Products
With Cytostatic Activity
Pp.1257-1277
A. Gryszkiewicz-Wojtkielewicz, I. Jastrzebska, J.W. Morzycki , and D. B. Romanowska
Abstracts
[Back to top] Plant Constituents with Hormonal Effects
Christian Terreaux, Johanne Polasek and Kurt Hostettmann
Phytohormones describe substances of plant origin with a hormonal activity. Epidemiological studies have shown a high health care potential for phytoestrogens. They are plant secondary metabolites with structural analogies to estradiol and with an influence on the estrogenic hormonal pathways. The main chemical classes are isoflavones, lignans, coumestans, prenylflavonoids and stilbene derivatives and occur in food and many health products. Soy and soy isoflavones represent an important source of phytoestrogens. Some human natural estrogens and androgens, or analogues, also occur in plants. Other hormones, such as melatonin, have also been found in plants.
[Back to top] Plant Substances as Antiviral Agents: An Update
(1997-2001)
P.
Cos , D. Vanden Berghe , T. De Bruyne , A.J. Vlietinck
Since our review in Current Organic Chemistry in 1997 (Curr. Org. Chem. 1997, 1, p. 307-344), important advances have been made in the field of natural products antiviral research. Therefore, we provide here a comprehensive review of the latest developments on plant substances as antiviral agents. The review is mainly focused on plant-derived substances with an anti-human immunodeficiency virus (anti-HIV) and an anti-herpes simplex virus (anti-HSV) activity.
The anti-HIV activity of the plant substances is discussed according to their mechanism of action, targeting the critical steps of the HIV replicative cycle, i.e. adsorption, virus-cell fusion, virus uncoating, reverse transcription, integration, proviral DNA transcription, transcription, translation, assembly, and budding. Some of the anti-HIV active compounds show also immune stimulating properties, which can provide an additional benefit in the treatment of AIDS. The anti-HSV activities of the plant substances are discussed according to their in vitro and in vivo activity against HSV-1 and HSV-2, including acyclovir-resistant strains, and where relevant, their activity against cytomegalovirus is mentioned. Finally, the antiviral activities of plant substances against the influenza virus are briefly outlined.
[Back to top] Brominated Diterpenes of Marine Origin
J.-M.
Kornprobst and H.-S. Al-Easa
Between 1971 and 2000, eighty brominated diterpenes were isolated from only two groups of marine organisms: red algae and gastropods, so it is likely that all bromoditerpenes only originate from Rhodophyceae and herbivorous molluscs which feed on them. Occurrence and general considerations on the encountered carbon skeletons are presented in the two first parts of this review. All brominated diterpenes are presented in third part with physicochemical properties and spectroscopic data available in the literature. The fourth part is devoted to biogenesis schemes for each carbon skeleton and the fifth part summarises the published data on biological activities of brominated diterpenes. This review covers the literature up to 2000; three new bromoditerpenes characterized in 2001 from two red algae are described in an addendum. This review ends with a general index for all mentioned compounds.
[Back to top] Recent Developments with 1,2,4-Trioxane-Type Artemisinin
Analogues
G.
Bez, B. Kalita, P. Sarmah, N.C. Barua
and D.K. Dutta
Artemisinin, a highly oxygenated sesquiterpene lactone endoperoxide isolated by Chinese researchers in 1971 has been found to be a superior plasmocidal and blood schizontocidal agent to conventional antimalarial drugs against malarial strains. Since then, an enormous amount of work has been done on this molecule by different groups covering aspects such as characterisation, total synthesis, understanding of the mechanism of action through QSAR studies, etc. which has unveiled tremendous amount of information about this molecule and resulted in a large number of published and patented literature. These studies have enabled scientists during the nineties to delineate the basic structural requirement - the 1,2,4-trioxane ring system as the essential pharmacophore. Since then a large number of simpler molecules containing mainly the core pharmacophore have been synthesized and evaluated against different malaria strains; many of which have shown even better plasmocidal activity than the parent molecule. Recent studies have also generated information on toxicity of some of the initial derivatives, viz. arteether, artemether, etc. A lot of efforts have been made to produce structural changes viz. synthesis of C-10 carba-analogues, ring-contracted derivatives, fluoro derivatives, simple 1,2,4-trioxanes etc. These studies aim to produce derivatives having maximum potency and minimum toxicity.
[Back to top] Approaches
Towards the Synthesis of Cephalostatins, Ritterazines and Saponins from
Ornithogalum saundersiae – New Natural Products With Cytostatic Activity
A. Gryszkiewicz-Wojtkielewicz, I. Jastrzebska, J.W. Morzycki , and D. B. Romanowska
Secondary metabolites of marine invertebrates continue to attract the attention of organic chemists, biochemists, and pharmacologists due to their novel structures and potent biological activities. One such example is cephalostatin 1 isolated from the Indian Ocean hemichordate Cephalodiscus gilchristi, which exhibited remarkable cytotoxic activity against a broad spectrum of malignant tumor cells. Similar marine alkaloids (e.g. ritterazine G) were found in the lipophilic extract of the tunicate Ritterella tokioka collected off the coast of Japan. These very potent compounds, cephalostatins and ritterazines, belong to the large family of trisdecacyclic pyrazines, consisting of two steroid units. The two steroid halves of cephalostatin 1 and other highly cytotoxic members of the family are different. The biological activity of the dimeric steroid-pyrazine marine alkaloids and their limited availability coupled with the new and intriguing structure make them an attractive challenge for the synthetic organic chemists. A few years ago a group of cholestane glycosides was isolated from the bulbs of Ornithogalum saundersiae, a species of the lily family without any medicinal folkloric background. Similar glycosides were recently isolated from Galtonia candicans. The major component of the mixture of saponins, OSW-1, exhibited sub-nanomolar antineoplastic activity. While OSW-1 is exceptionally cytotoxic against various tumor cells, it showed little toxicity to normal human pulmonary cells. The cytotoxicity profile of OSW-1 against different cancer cell lines was found to be surprisingly similar to that of the cephalostatins, which appears to imply a related mechanism of action. In this review article the synthetic efforts towards these compounds are described.