Cytotoxic terpenoids from Nardophyllum bryoides

Sánchez, Marianela; Mazzuca, Marcia; Veloso, María José; Fernández, Liliana Patricia; Siless, Gastón Ezequiel; Puricelli, Lydia; Palermo, Jorge Alejandro

doi:10.1016/j.phytochem.2010.04.019

Cited by 19 publications

(25 citation statements)

References 9 publications

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“…In addition, CYP716A2 catalyzed the C-22a hydroxylation of a-amyrin and b-amyrin, a catalytic activity that has not been previously reported. The main product of aAS and CYP716A2 co-expressing yeast, 22a-hydroxy-a-amyrin, was previously isolated from Nardophyllum bryoides as a cytotoxic compound against an LM3 (murine lung adenocarcinoma) cell line [18]. Interestingly, while the presence of 22a-hydroxy-a-amyrin in A. thaliana is unknown, our discovery allows us to produce this bioactive compound by using a heterologous yeast expression system.…”

Section: Discussionmentioning

confidence: 92%

Novel triterpene oxidizing activity of Arabidopsis thaliana CYP716A subfamily enzymes

et al. 2016

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Edited by Ulf-Ingo Fl€ uggeTriterpenoids have diverse chemical structures and bioactivities. Cytochrome P450 monooxygenases play a key role in their structural diversification. In higher plants, CYP716A subfamily enzymes are triterpene oxidases. In this study, Arabidopsis thaliana CYP716A1 and CYP716A2 were characterized by heterologously expressing them in simple triterpene-producing yeast strains. In contrast to the C-28 oxidative activity of CYP716A1 shown in several CYP716A subfamily enzymes, remarkably, CYP716A2 displayed 22a-hydroxylation activity against a-amyrin that has not been previously reported, which produces the cytotoxic triterpenoid, 22a-hydroxy-a-amyrin. Our results contribute to the enrichment of the molecular toolbox that allows for the combinatorial biosynthesis of diverse triterpenoids.Keywords: 22a-hydroxylation; Arabidopsis thaliana; combinatorial biosynthesis; CYP716A; cytochrome P450 monooxygenase; triterpenoids HighlightsThe full-length CDS of CYP716A2, miss-annotated on TAIR, is successfully cloned. Novel 22a-hydroxylation activity of CYP716A subfamily enzymes is reported. The chemical structure of 22a-hydroxy-a-amyrin is confirmed by NMR analysis.Triterpenoids represent one of the largest groups of plant specialized metabolites and are composed of six C5 (isopentenyl diphosphate) units [7]. Their carbon skeletons are synthesized from the common precursor 2,3-oxidosqualene by oxidosqualene cyclases (OSCs), and these skeletons are further oxidized by cytochrome P450 monooxygenases (P450s) and glycosylated by UDP-dependent glycosyltransferases (UGTs), which generate diverse triterpenoid/triterpenoid saponin structures [17,19]. Around 80 OSCs, 30 P450s, and 10UGTs are reportedly involved in triterpenoid biosynthesis in plants [22,25]. Among them, P450s have been described as the key players in diversifying triterpenoid scaffolds, and were recently identified in many triterpenoid-producing plant species [22]. For example, CYP88D6 and CYP72A154 from Glycyrrhiza uralensis were identified as components in the biosynthesis of glycyrrhetinic acid, the aglycone of glycyrrhizin [20,21]. In addition, CYP716A12 and other CYP716A subfamily enzymes have been identified as multifunc-

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Section: Discussionmentioning

confidence: 92%

Novel triterpene oxidizing activity of Arabidopsis thaliana CYP716A subfamily enzymes

et al. 2016

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“…In this context, Nardophyllum bryoides (Chiliotricum group, Asteraceae), a widely distributed shrub in Argentinean and Chilean Patagonia and the Andes (Jakupovic et al, 1986;Bonifacino, 2005) was selected to evaluate its possible antifouling activity. In previous studies, some metabolites isolated from this species have shown moderate cytotoxic activity against human pancreatic adenocarcinoma cell lines (Sánchez et al, 2010) and strong trypanocidal effect (Siless et al, 2013). Also, the extracts from another species of this genus, Nardophyllum armatum, showed antioxidant, antibacterial, antirheumatic and antifungal activity.…”

Section: Introductionmentioning

confidence: 92%

“…Plant natural products from abundant and widely distributed species represent an attractive and sustainable source of new bioactive compounds. Terrestrial plants produce secondary metabolites that exhibit a variety of biological activities, many of which are of considerable significance to humans (Sánchez et al, 2010). It is worth noting that some plant extracts have shown antifouling activity, e.g.…”

Section: Introductionmentioning

confidence: 99%

Effect of secochiliolide acid isolated from the Patagonian shrub Nardophyllum bryoides as active component in antifouling paints

Pérez

Garcia

Sánchez

et al. 2014

International Biodeterioration & Biodegradation

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Environmental concerns about the use of toxic antifoulants have led to an increased interest in the development of new alternatives. So far, most of the antifouling natural products have been obtained from marine organisms. However, some secondary metabolites from terrestrial plants could be promising antifoulant candidates. The antifouling performance of secochiliolide acid, the main component isolated from Nardophyllum bryoides ethanolic extract, was evaluated for inclusion in rosin-based coatings. Field testing was conducted during the summer months at Mar del Plata harbor, Argentina. The results indicated that secochiliolide acid-based paints completely inhibited the settlement of Bugula neritina colonies, Polydora sp., Hydroides elegans, Corophium sp. and solitary ascidians, and also reduced the attachment of some algae as Enteromorpha intestinalis and Ectocarpus sp. In addition, a lower density and diversity of microfouling species was registered. These results highlighted the importance of terrestrial plants as a sustainable source of potential environmentally friendly antifoulants.

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“…[3,4] NTDs can be controlled, prevented and/or eliminated; however, the current available treatments show limited effectiveness, with increased resistance development and/or high toxicity. [6,7] This compound is present in the aerial parts of this plant and belongs to the seco-ent-halimane family, its spirolactone moiety is a remarkable feature, which is a fragment present in several natural trypanocidal compounds. [1] Nature continues to be the main source of structural diversity in molecular terms, which, in the pursuit of multidisciplinary collaborative research, can lead to the discovery of new prototype compounds, some of which may be developed into commercial drugs.…”

Section: Introductionmentioning

confidence: 99%

Secochiliolide ester derivatives: Preparation and evaluation of their antitrypanosomal and antimalarial efficacy

et al. 2018

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In the present study, a series of new esters of secochiliolide acid (SA), a diterpene isolated from Nardophyllum bryoides, were synthesized in good yield. All compounds were evaluated for their in vitro antiparasitic properties (on Plasmodium falciparum and Trypanosoma brucei brucei) and cytotoxicity (on WI38, normal mammalian cells). They displayed moderate antitrypanosomal activity with IC values between 2.55 and 18.14 μm, with selectivity indices >10, and low antiplasmodial effects with IC > 29 μm. The only exception was the n-hexyl ester of SA, which showed a strong and selective antiplasmodial activity (IC = 1.99 μm and selectivity index = 117.0). The in vivo antimalarial efficacy of this compound was then assessed according to the 4-day suppressive test of Peters in mice. An intraperitoneal treatment at 50 mg kg day induced a slight parasitaemia reduction by 56% which was statistically significant on day 4 post-infection and an increase in the survival time.

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Cytotoxic terpenoids from Nardophyllum bryoides

Cited by 19 publications

References 9 publications

Novel triterpene oxidizing activity of Arabidopsis thaliana CYP716A subfamily enzymes

Novel triterpene oxidizing activity of Arabidopsis thaliana CYP716A subfamily enzymes

Effect of secochiliolide acid isolated from the Patagonian shrub Nardophyllum bryoides as active component in antifouling paints

Secochiliolide ester derivatives: Preparation and evaluation of their antitrypanosomal and antimalarial efficacy

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