Britannin — A lactone fromInula britannica

Rybalko, K. S.; Шейченко, В. И.; Maslova, G. A.; Kiseleva, E. Ya.; Gubanov, I. A.

doi:10.1007/bf00571147

Cited by 5 publications

(3 citation statements)

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“…As mentioned above, BRT was first isolated from a flowering sample of I. britannica collected in the Muyunmum desert (Jambyl region, southern Kazakhstan) in 1968 by Russian scientists [9]. The compound was identified as a sesquiterpene lactone and its structure was elucidated a few years later by the same authors [12].…”

Section: Discovery Structural Characterization and Synthesis Of Brtmentioning

confidence: 97%

“…The plant genus Inula (Asteraceae) comprises more than 100 species distributed worldwide (www.theplantlist.org, accessed on 25 September 2021). BRT was first isolated from I. britannica L. in 1968 [9,12,13], but later the product was found in other Inula species [14], such as I. aucheriana DC. [15] and I. japonica Thunb.…”

Section: Inula Species Producing Brt and Their Medicinal Usesmentioning

confidence: 99%

“…The subclass also includes analogues such as mexicanin I, damsin and neoambrosin [6][7][8]. Another important member of the group is britannin (BRT in Figure 2), initially isolated from the plant Inula britannica L. [9]. These compounds have been characterized as inhibitors of the transcription factor NFκB, due to the targeting of a cysteine residue of the p65 subunit by the α-methylene-γ-butyrolactone moiety [10,11].…”

Section: Introductionmentioning

confidence: 99%

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Anticancer Targets and Signaling Pathways Activated by Britannin and Related Pseudoguaianolide Sesquiterpene Lactones

Bailly

2021

Biomedicines

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Sesquiterpene lactones (SLs) are abundant in plants and display a large spectrum of bioactivities. The compound britannin (BRT), found in different Inula species, is a pseudoguaianolide-type SL equipped with a typical and highly reactive α-methylene-γ-lactone moiety. The bioproperties of BRT and related pseudoguaianolide SLs, including helenalin, gaillardin, bigelovin and others, have been reviewed. Marked anticancer activities of BRT have been evidenced in vitro and in vivo with different tumor models. Three main mechanisms are implicated: (i) interference with the NFκB/ROS pathway, a mechanism common to many other SL monomers and dimers; (ii) blockade of the Keap1-Nrf2 pathway, with a covalent binding to a cysteine residue of Keap1 via the reactive α-methylene unit of BRT; (iii) a modulation of the c-Myc/HIF-1α signaling axis leading to a downregulation of the PD-1/PD-L1 immune checkpoint and activation of cytotoxic T lymphocytes. The non-specific reactivity of the α-methylene-γ-lactone moiety with the sulfhydryl groups of proteins is discussed. Options to reduce or abolish this reactivity have been proposed. Emphasis is placed on the capacity of BRT to modulate the tumor microenvironment and the immune-modulatory action of the natural product. The present review recapitulates the anticancer effects of BRT, some central concerns with SLs and discusses the implication of the PD1/PD-L1 checkpoint in its antitumor action.

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Section: Discovery Structural Characterization and Synthesis Of Brtmentioning

confidence: 97%

Section: Inula Species Producing Brt and Their Medicinal Usesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Anticancer Targets and Signaling Pathways Activated by Britannin and Related Pseudoguaianolide Sesquiterpene Lactones

Bailly

2021

Biomedicines

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Amination Products of Inula britannica Lactones and Their Antitumor Activity

et al. 2015

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The reactions with amines of the sesquiterpene lactones britanin and inuchinenolide C isolated from Inula britannica were studied. Migration of the acetyl group during the addition reaction was observed and depended on the nature of the amine and solvent. Compounds with antitumor activity were found among the new amine derivatives.The genus Inula (Asteraceae) comprises about 100 plants, many of which are widely used in folk medicine owing to a variety of biological activities [1] including anti-inflammatory, antitumor, and bactericidal [2]. Plants of this genus contain a large number of physiologically active compounds, e.g., sesquiterpene lactones, among which compounds with valuable biological properties were observed [3].The sesquiterpene lactone britanin (1) is frequently encountered in plants of the genus Inula and was isolated from I. caspica Blume, I. britannica L., and I. aspera Poir.[4]. Its pseudoguaianolide structure was first described over 50 years ago [5]. An x-ray crystal structure analysis [6] established the R-configuration for the 2-acetoxy group. ** We also obtained a significant quantity of a britanin isomer during its isolation by the previously described method [7]. This was inuchinenolide C (2), which was first isolated from I. britannica var. chinensis and differed in the position of the acetyl group [8]. Despite the similar structures, 1 and 2 were easily differentiated by the positions of the resonances for the 4-and 6-protons in the PMR spectrum.Chemical modifications of 1 that affected the five-and seven-membered rings included acylation and deacetylation [9] and oxidation [9, 10]. However, 1 and 2 also include a highly reactive electrophilic center as an exomethylene in the lactone ring that is susceptible to attack by nucleophiles. The reaction of 1 with methylmercaptoacetate (S-nucleophile) is known to occur at the lactone ring and to produce addition products at the C-11 and C-13 atoms in a 3:1 ratio [11]. Examples of the addition of N-nucleophiles to britanin isolated from I. caspica are known. According to some researchers [12][13][14], the reaction with secondary (diethylamine and morpholine) and primary (ethanolamine) amines in addition to bifunctional ethylenediamine occurred stereospecifically. However, the physicochemical properties of the products were not characterized in those studies. Furthermore, these reactions with 2 have not been reported. Recently, compounds with various biological activities, including antitumor activity, were observed among sesquiterpene lactone amine derivatives [15]. This is responsible for the heightened interest in such compounds.We studied the reaction of 1 with several primary aliphatic and secondary amines, including heterocyclic ones, in order to prepare new amine derivatives. The reaction proceeded readily in a polar protic (MeOH) or nonpolar aprotic (CH 2 Cl 2 ) solvent at room or slightly elevated temperature. The structures of the reaction products depended on the reaction conditions and the nature of the amine (basicity and nucleophil...

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