Sesquiterpene lactones examples

Classical examples of anti-inflammatory Asteraceae are Arnica montana and Calendula officinalis, both used in European medicine to treat bruises and contusions. There is an expanding body of evidences to suggest that Asteraceae could be a useful source of anti-inflammatories, such as sesquiterpene lactones and/or triterpene alcohols, the latter being known to inhibit 12-O-tetra-decanoylphorbol-13-acetate (TPA)-induced inflammation in mice as efficiently as commercial indomethacine by possible inhibition of phospholipase A2 (10). 

The family Asteraceae is a prolific source of sesquiterpene lactones, among which, melampolides have been shown to inhibit the enzymatic activity of elastases. Melampolides are a common member of the Melampodi-inae subtribe. Examples of medicinal Asteraceae known to elaborate melampolides are Sigesbeckia orientalis L. and Mikania cordata (Burm.f.) B.L. Robinson. 

There is an expanding body of evidence to suggest that sesquiterpene lactones inhibit the synthesis NO synthetase. One such compound is an ambrosanolides-type sesquiterpene known as cumanin characterized from Ambrosia psilostachya. This sesquiterpene inhibit the enzymatic activity of NO synthetase with an IC50 value of 9.38 xM (49). Another example is the well-known artemisinin, a sesquiterpene used as an alternative drug in the treatment of severe and multidrug-resistant malaria, which inhibits NO synthesis in cytokine-stimulated human astrocytoma T67 cells (50). 

A (4) and B (5) structures originally presented [15] were wrong and that these compounds do not occur in feverfew. Canin (19) is an example of a guainolide-type sesquiterpene lactone. 

Other phenolic compounds of commercial importance include the terpenoids, including mono, di, tri, and sesquiterpenes. While most of these are used as essential oils, fragrances, and flavors in various products, they are toxins in certain species. For example the sesquiterpene lactones of the Centaurea species cause an irreversible Parkinson s-like condition in horses called nigro-pallidal encephalomalacia. This is a lethal condition and the prognosis for recovery is grave in most cases, affected horses should be euthanized before reaching the terminal stages. 

Ultrasound-assisted extraction is a rapid technique that can also be used with mixtures of immiscible solvents hexane with methanol-water (9 1), for example, is a system used for the Brazilian plant Lychnophora ericoides (Asteraceae). The hexane phase concentrated less polar sesquiterpene lactones and hydrocarbons, while the aqueous alcohol phase concentrated flavonoids and more polar sesquiterpene lactones. 

The biological activity and toxicity of terpenoids to herbivores has been discussed (56,84) and representatives of each major type of terpene are known to be active. Well known examples are sesquiterpene lactones, pyrethrins, and several classes of diter-penes and triterpenes. 

A number of sesquiterpenes have been demonstrated to have pronounced biological activity ( ) among the non-volatile compounds the sesquiterpene lactones are best known (M) but other oxygenated sesquiterpenes are also known to be active. For example, the role of gossypol, a dimeric sesquiterpene and structurally related compounds has been investigated (21,22). The oxygenated sesquiterpenes, shiromodiol monoacetate and diacetate, from Parabenzoin trilobum (=Lindera triloba Blume) possess potent anti feeding activity toward Spodoptera litura larvae (85). 

The nucleophilic properties of groups such as -NHR and -SH have been reported in natural Michael acceptor systems present in many natural products. Typical examples are the addition of the sulfhydryl groups of glutathione to the exocyclic methylene of sesquiterpene lactones (Fig. 6.7).14,41 Such interactions have been considered as responsible for the biological activity observed in many natural products, and this is again the case in Zwanenburg s hypothesis for strigolactones. 

Often used in concert with mass spectrometry, NMR spectroscopy remains an invaluable structural diagnostic tool of particular importance to tricyclic natural products chemistry. For example, the tricyclic phenolic compound moracin P (3) was one of eight previously known compounds identified together with two new isoprenoid-substituted flavanones in isolates of the root bark of mulberry trees <89H(29)807>. In a series of studies of 6-7-5 tricyclic natural products, ID and 2D H and l3C NMR spectroscopy were employed extensively in the structure determination of sesquiterpene lactones (4)—(8) found among the aerial natural products of toxic plants (85P1378,90P551, 90P3875). 

There are many examples in the literature for applications of LC-NMR in the pharmaceutical industry. In the area of natural products, LC-NMR has been applied to screen plant constituents from crude extracts [54,57,67,68] and to analyze plant and marine alkaloids [69-72], flavonoids [73], sesquiterpene lactones [74,75], saponins [58,76], vitamin E homologues [77], and antifungal and bacterial constituents [56,78,79] as examples. In the field of drug metabolism, LC-NMR has been extensively applied for the identihcation of metabolites [42, 80-88] and even polar [89] or unstable metabolites [43]. And hnally, LC-NMR has been used for areas such degradation products [90-93], drug impurities [94-102], drug discovery [103,104], and food analysis [105-107]. 

There are two reasons for the great interest being shown in artemisinin and its derivatives. First, there is little cross resistance with Plasmodium falciparum between the members of this series and the quinoline-based antimalarials like chloroquine (203). On the contrary, significant potentiation of effect is observed in combination with chloroquine analogs such as mefloquine (204). Second, the high lipid solubility of, for example, arte-mether ensures rapid penetration into the CNS, so these sesquiterpene lactones are first-... 

Examples of other antimicrobial sesquiterpene lactones from the Anthemideae tribe also included those isolated from Anaphalis margaritacea (L.) Benth Hook., Fig. (24) [196], two new antibacterial melampolide-type sesquiterpene lactones from Smallanthus sanchifolius (Poepp. and Endl.) H. Robinson, which exhibited potent antimicrobial activity against Bacillus subtilis and Pyricularin oryzae [197], and six... 

New Zealand liverwort Schistochila glaucescens produced three known bisbibenzyls, viz neomarchantins A and B, and marchantin C (813), with two unprecedented sesquiterpenes bisbibenzyls Glaucescens Bis Bibenzyl (GBB) A and (GBB) B (295 and 296), the first examples of a bisbibenzyl having a sesquiterpene moiety. A biosynthetic route to sesquiterpene lactone glaucescenolide, GBB A and GBB B (295 and 296), via a shared furanosesquiterpene intermediate, is proposed [148]. 

An example of the power of this method in structure elucidation is shown for the sesquiterpene lactone acetylisomontanolide (Fig. 5.74). The complete carbon skeleton of the molecule can be traced directly in the spectrum, with breakdown occurring only when heteroatom linkages arise. Unfortunately, it is rare indeed to have sufficient sample quantities at hand to consider employing this technique, and still it remains a little used method in its original form. However, greater potential exits for directly tracing carbon-carbon connectivities with recently developed methods based on proton excitation and observation combined with gradient selection see Section 5.8.4 below. 

Horeau and Kagan5 applied the method to a large number of steroids and found that it led to the correct configurations. It has been applied successfully to terpencs, -2 to caryophyllene derivatives,6 to grayanotoxin-I (1) and related toxins,7 and to sesquiterpene lactones,8 for example (2). 

Certain natural products indirectly induce ER stress. For example, agents that disrupt the functions of the Golgi apparatus can induce ER stress. Additionally, the plant-derived (Thapsiagarganicd) sesquiterpene lactone thapsigargin (5) is an ATPase inhibitor, which inhibits intracellular Ca transport and is also used as a probe to study ER stress. 

In Ebadi s Chapter 23, the plant family Compositae or Asteraceae is said to contain members that have antitumor action. Among the classes of compounds present are the sesquiterpene lactones (SQLs), associated with antitumor activity, for example, the substance known as parihenin. 

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