New sesquiterpene lactones from Elephantopus mollis and their leishmanicidal activities.
TL;DR: The alpha-methylene-gamma-butyrolactone moiety was found to be essential to the potent leishmanicidal effect observed and exhibited potent in vitro leish manicidal activities against Leishmania major.
Abstract: The leishmanicidal compounds isolated from whole plants of Elephantopus mollis H.B.K. were identified as follows. Three new sesquiterpenoid lactones, 2,5-epoxy-2beta-hydroxy-8alpha-(2-methylpropenoyloxy)-4(15),10(14),11(13)-germacratrien-12,6alpha-olide, (4betaH)-8alpha-(2-methylpropenoyloxy)-2-oxo-1(5),10(14), 11(13)-guaiatrien-12,6alpha-olide and (4betaH)-5alpha-hydroxy-8alpha-(2-methylpropenoyloxy)-1(10),11(13)-guaiadiene-12,6alpha-olide, were isolated from Peruvian and Brazilian collections together with four known sesquiterpenoids, molephantin, elephantopin, isoelephantopin and 2-deethoxy-2beta-methoxyphantomolin. They exhibited potent in vitro leishmanicidal activities against Leishmania major. The alpha-methylene-gamma-butyrolactone moiety was found to be essential to the potent leishmanicidal effect observed.
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TL;DR: A review of the literature on plant extracts and chemically defined molecules of natural origin showing antileishmanial activity and some aspects of recent antileishesmanial-activity-directed research on natural products are discussed.
414 citations
TL;DR: The current review attempts to give an overview on the potential of such plant-derived natural products as antiprotozoal leads and/or drugs in the fight against NTDs.
Abstract: Infections with protozoan parasites are a major cause of disease and mortality in many tropical countries of the world. Diseases caused by species of the genera Trypanosoma (Human African Trypanosomiasis and Chagas Disease) and Leishmania (various forms of Leishmaniasis) are among the seventeen "Neglected Tropical Diseases" (NTDs) defined by the WHO. Furthermore, malaria (caused by various Plasmodium species) can be considered a neglected disease in certain countries and with regard to availability and affordability of the antimalarials. Living organisms, especially plants, provide an innumerable number of molecules with potential for the treatment of many serious diseases. The current review attempts to give an overview on the potential of such plant-derived natural products as antiprotozoal leads and/or drugs in the fight against NTDs. In part I, a general description of the diseases, the current state of therapy and need for new therapeuticals, assay methods and strategies applied in the search for new plant derived natural products against these diseases and an overview on natural products of terpenoid origin with antiprotozoal potential were given. The present part II compiles the current knowledge on natural products with antiprotozoal activity that are derived from the shikimate pathway (lignans, coumarins, caffeic acid derivatives), quinones of various structural classes, compounds formed via the polyketide pathways (flavonoids and related compounds, chromenes and related benzopyrans and benzofurans, xanthones, acetogenins from Annonaceae and polyacetylenes) as well as the diverse classes of alkaloids. In total, both parts compile the literature on almost 900 different plant-derived natural products and their activity data, taken from over 800 references. These data, as the result of enormous efforts of numerous research groups world-wide, illustrate that plant secondary metabolites represent an immensely rich source of chemical diversity with an extremely high potential to yield a wealth of lead structures towards new therapies for NTDs. Only a small percentage, however, of the roughly 200,000 plant species on earth have been studied chemically and only a small percentage of these plants or their constituents has been investigated for antiprotozoal activity. The repository of plant-derived natural products hence deserves to be investigated even more intensely than it has been up to present.
231 citations
Cites background from "New sesquiterpene lactones from Ele..."
...Some simple structure-activity relationships could be established; most importantly the dependence of activity on the presence of an α,β-unsaturated exocyclic methylene lactone group, well known to be important for many other biological activities of STLs (overview see [100, 292]) was proven also for antileishmanial activity [291]....
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...A variety of germacranolides of different structural subclasses and some guaianolides isolated from Elephantopus mollis were reported to possess high activity against Lmaj promastigotes [291]....
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TL;DR: This review highlights the potential that remains untapped in natural products as drug leads for NTDs, and covers natural products from plant, marine, and microbial sources including natural-product-inspired semi-synthetic derivatives which have been evaluated against the various causative agents of N TDs.
Abstract: Endemic in 149 tropical and subtropical countries, neglected tropical diseases (NTDs) affect more than 1 billion people annually, including 875 million children in developing economies. These diseases are also responsible for over 500,000 deaths per year and are characterized by long-term disability and severe pain. The impact of the combined NTDs closely rivals that of malaria and tuberculosis. Current treatment options are associated with various limitations including widespread drug resistance, severe adverse effects, lengthy treatment duration, unfavorable toxicity profiles, and complicated drug administration procedures. Natural products have been a valuable source of drug regimens that form the cornerstone of modern pharmaceutical care. In this review, we highlight the potential that remains untapped in natural products as drug leads for NTDs. We cover natural products from plant, marine, and microbial sources including natural-product-inspired semi-synthetic derivatives which have been evaluated against the various causative agents of NTDs. Our coverage is limited to four major NTDs which include human African trypanosomiasis (sleeping sickness), leishmaniasis, schistosomiasis and lymphatic filariasis.
143 citations
TL;DR: The Sultanate of Oman’s Medicinal Plants and Marine Natural Products, University of Nizwa, and South Africa Department of Pharmaceutical and Biological Chemistry, UCL School of Pharmacy, London WC1N 1AX, United Kingdom.
Abstract: 2011 Hidayat Hussain,*,† Ahmed Al-Harrasi,*,† Ahmed Al-Rawahi,† Ivan R. Green,‡ and Simon Gibbons* †UoN Chair of Oman’s Medicinal Plants and Marine Natural Products, University of Nizwa, P.O. Box 33, Birkat Al Mauz, Nizwa 616, Sultanate of Oman ‡Department of Chemistry and Polymer Science, University of Stellenbosch, Private Bag X1, Matieland, Stellenbosch 7600, South Africa Department of Pharmaceutical and Biological Chemistry, UCL School of Pharmacy, London WC1N 1AX, United Kingdom
118 citations
TL;DR: The present chapter attempts to present an overview on the current knowledge on structure-activity relationships of STLs of different types and different activities.
Abstract: Sesquiterpene lactones (STLs) are one of the largest biogenetically homogenous groups of natural products known. Currently, the Dictionary of Natural Products holds a total of over 11000 entries on sesquiterpenes, of which almost 5000 contain at least one lactone group. One reason for the large number of individual compounds and the associated structural diversity of this class of natural products is most certainly related to their enormously broad spectrum of biological activities, rendering them a highly valuable defense tool for those organisms synthesizing them. It is thus no surprise that the plant family from which most STLs have been isolated, i.e. the Compositae, is among the largest and ecologically most diverse plant families on our planet. Many of the biological activities of the most common types of STLs are known to be mediated by a simple general chemical mechanism, i.e. alkylation of biological macromolecules in terms of Michael type additions. These effects have been surveyed in numerous comprehensive reviews. Moreover, some very specific receptor-mediated activities of less frequent types of STLs are known. Quite surprisingly, despite the plethora of reports on STL bioactivity, only very few systematic studies on structure-activity relationships have been carried out. Detailed studies of this kind, however, would be highly desirable with respect to several aspects of medicinal/pharmaceutical, agrochemical and ecological interest. Most importantly, many STL-containing plants have been used in traditional medicines of all cultures for many centuries and continue to be utilized also in modern phytotherapy. Therapeutic use of STLs as pure chemicals is - in spite of their broad utilization in form of plants or crude extracts-restricted to very few examples, which is mainly due to a lack of knowledge on the structural requirements for selectivity with respect to a desired biological activity. It may, however, be conceived, that STLs could play a valuable role as lead structures to new therapeutic agents, if more information, especially in the form of quantitative structure-activity relationships (QSAR), existed. The present chapter attempts to present an overview on the current knowledge on structure-activity relationships of STLs of different types and different activities. Selected examples of current research in the author’s laboratory on structure-reactivity- and structure-activity relationships of STLs are presented.
104 citations