The genus Inula and their metabolites: from ethnopharmacological to medicinal uses.

Medicinal chemistry strategies to discover P-glycoprotein inhibitors: An update.

Sesquiterpene lactones (STLs) present a wide range of biological activities, mostly based on their alkylating capabilities, which underlie their therapeutic potential. These compounds are the active constituents of a variety of plants, frequently used as herbal remedies. STLs such as artemisinin and its derivatives are in use as first-line antimalarials while others, such as parthenolide, have recently reached cancer clinical trials. However, the toxicological profile of these compounds must be thoroughly characterized, since the same properties that make STL useful medicines can also cause severe toxicity. STL-containing plants have long been known to induce a contact dermatitis in exposed farm workers, and also to cause several toxic syndromes in farm animals. More recently, concerns are been raised regarding the genotoxic potential of these compounds and the embryotoxicity of artemisinins. A growing number of STLs are being reported to be mutagenic in different in vitro and in vivo assays. As yet no systematic studies have been published, but the genotoxicity of STLs seems to depend not so much on direct DNA alkylation as on oxidative DNA damage and other partially elucidated mechanisms. As the medicinal use of these compounds increases, further studies of their toxic potential are needed, especially those focusing on the structural determinants of genotoxicity and embryotoxicity.

Sesquiterpene lactones: Adverse health effects and toxicity mechanisms

Introduction: The plants of the genus Inula (Asteraceae) are widely distributed throughout Europe, Africa and Asia, and many of these plants have long been used in folk medicine. This genus is a rich source of sesquiterpenoids, which exhibit a wide range of biological activities. Recently, a series of bioactive sesquiterpenoid dimers, with unusual carbon skeletons, have been reported and these have gathered considerable interest. Areas covered: This article systematically reviews sesquiterpenoids isolated from the genus Inula that have appeared in literature up to August 2013, critically highlighting their anti-tumoral activities and relevant mechanistic insights. The authors also discuss the initial structure–activity relationships for the cytotoxic and anti-tumoral activities of the Inula sesquiterpenoids. Finally, the authors discuss the challenges and potential applications of these sesquiterpenoids in the future. Expert opinion: Cytotoxic and anti-tumor activities of Inula sesquiterpenoids have been ...

Inula sesquiterpenoids: structural diversity, cytotoxicity and anti-tumor activity

Biopesticides offer a more sustainable solution to pest control than synthetic alternatives. As chemical pesticides are withdrawn owing to resistance problems or because they are no longer commercially viable, an opportunity arises for biorational solutions. Biopesticides do not feature residue problems which are a matter of significant concern for consumers. However, biopesticides are not as effective as chemicals. Compatibility with synthetic pesticides varies and shelf life is often shorter. Considering the growing demand for organic production of food and registration-related problems, the number of pest management products that can be used in this sort of production is limited. Natural product-based search strategies have had some notable successes. The pesticide industry’s natural product search efforts to date have concentrated on compounds of microbial origin primarily from non-pathogenic soil microbes. Less effort has been put into the search for pesticides of plant origin. Bioassay-directed isolation has been the preferred search method once a producing organism has been selected. This laborious approach often leads to the rediscovery of known compounds. Modern tandem separation/chemical characterization instrumentation can eliminate much of this problem by identifying compounds before they are bioassayed. Pesticide search strategies discovery are no different from drug research. The dominant and most successful strategy has been that of systematically screening large numbers of synthetic compounds followed by the structure optimization of lead compounds. The biorational approach entailing the design of inhibitors of specific molecular target sites was in vogue for several years. Using natural products as pesticides or as leads for new ones has had intermediate success. New tools have supported each of these strategies. For example, combinatorial chemistry combined with chemical diversity theory and high throughput screening allows for swifter production and testing of synthetic compounds. Similarly, new technologies have significantly improved the speed with which natural products can be discovered and evaluated for biological activities.

Natural Product-Based Biopesticides for Insect Control

Sesquiterpene lactones from Inula falconeri, a plant endemic to the Himalayas, as potential anti-inflammatory agents.

A new phenylpropanoid derivative (1), along with five phenylpropanoids (2-6), two monoepoxy lignans (8-9), one bisepoxy lignan (10), two cyclolignans (11-12), six neolignans (7, 13-17), two mixed lignan-neolignans (18-19), two lignan glycosides (20-21), and four flavonolignans (22-25), were isolated from the stems and twigs of Euonymus acanthocarpus. Compounds 2-3, 6-8, 12, and 14-25 were obtained from Celastraceae family for the first time, and compounds 5 and 9 were isolated from Euonymus genus for the first time. All the compounds were tested for cytotoxicity against SK-OV-3 and MCG-803 human tumor cell lines. Compounds 3, 10, 12, and 18 showed weak cytotoxicity against SK-OV-3 cell line, and compounds 3-4, 10-13, and 19 showed weak cytotoxicity against MCG-803 cell line.

Phenylpropanoids and lignanoids from Euonymus acanthocarpus

Chemical constituents of plants from the genus Euonymus.

The phytochemical investigation of the ethanolic extract of the whole plants of Geum japonicum Thunb. var. chinense F. Bolle yielded four new compounds: 20 β,28-epoxy-28-hydroxytaraxasteran-3 β-ol (1), (7R,8R)-4-hydroxy-9'-O-(α-L-rhamnopyranosyl)-3,3',5'-trimethoxy-8-O-4'-neolignan (2), (7R,8S)-4-hydroxy-9'-O-(α-L-rhamnopyranosyl)-3,3',5'-trimethoxy-8-O-4'-neolignan (3), and (7S,8S)-5-methoxycupressoside A (4), as well as 40 other known compounds. Structures were elucidated by physical, chemical, and spectroscopic methods, including 1D and 2D NMR, HRESIMS, and CD experiments. The taraxasterane-type triterpene (1) and lignans (2- 6) are reported for the first time from the GEUM genus. Moreover, all compounds were evaluated for anti-inflammatory activities against NO production in RAW264.7 macrophages, and only moderate activities were detected.

Fei Zhang

Papers

Sesquiterpene lactones from Inula falconeri, a plant endemic to the Himalayas, as potential anti-inflammatory agents.

Phenylpropanoids and lignanoids from Euonymus acanthocarpus

Chemical constituents of plants from the genus Euonymus.

Taraxasterane-type triterpene and neolignans from Geum japonicum Thunb. var. chinense F. Bolle

Terpenoids from Inula sericophylla Franch. and their chemotaxonomic significance