Anti-trypanosomal cadinanes synthesized by transannular cyclization of the natural sesquiterpene lactone nobilin

Mieri, Maria De; Kaiser, Marcel; Brun, Reto; Thormann, Ursula; Imanidis, Georgios; Hamburger, Matthias

doi:10.1016/j.bmc.2015.02.005

Cited by 6 publications

(15 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We began our study by treating compound 2 with p -toluensulfonic acid ( p -TsOH·H 2 O), a mild acid that has been extensively used to induce transannular cyclization in germacradiene derivatives [ 8 , 16 ]. After 1 h at room temperature, compound 5 (50%) and an inseparable mixture of 6 and 7 in a 3:2 ratio (10%) were obtained ( Scheme 2 ).…”

Section: Resultsmentioning

confidence: 99%

“…Close inspection of the NMR data revealed that 15 was the 3-hydroxy derivative of a cadinane that had been previously obtained by a reaction of nobilin with acids, whereby the transannular cyclization of the 1(10) double bond was facilitated by the alkyl–oxygen cleavage of the lactone ring. The reaction led to the formation of a single bond, C-5/C-10, which transformed the cyclodecadiene into a decaline ring system [ 7 , 8 ].…”

Section: Resultsmentioning

confidence: 99%

“…We recently reported on the spontaneous rearrangement of nobilin 1 , an E , Z -germacranolide isolated from the flowers of Roman chamomile ( Anthemis nobilis ) in aqueous media under physiological conditions [ 7 ]. We then investigated the rearrangement of 1 in aqueous and organic acidic media and found a transformation into various cadinane derivatives [ 8 ]. In the present study we investigated the rearrangement of epoxy derivatives 2 – 4 of nobilin ( 1 ) under acidic conditions.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Acid-Induced Rearrangement of Epoxygermacranolides: Synthesis of Furanoheliangolides and Cadinanes from Nobilin

et al. 2017

Self Cite

View full text Add to dashboard Cite

The acid-induced rearrangement of three epoxyderivatives of nobilin 1, the most abundant sesquiterpene lactone in Anthemis nobilis flowers, was investigated. From the 1,10-epoxyderivative 2, furanoheliangolide 5 was obtained, while the 4,5-epoxy group of 3 did not react. Conversely, when the 3-hydroxy function of nobilin was acetylated (12), the 4,5-epoxy derivative did cyclize into cadinanes (15 and 16) under Lewis acid catalysis. The reactivity of the 4,5- and 1,10-epoxy derivatives of nobilin (2 and 3) was compared with that of parthenolide, and rationalized on the basis of quantum chemical calculations. All isolated reaction products were fully characterized by spectroscopic and computational methods, and their in vitro anti-protozoal activity was evaluated. The paper could provide new insights into the biosynthesis of this class of natural products.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Acid-Induced Rearrangement of Epoxygermacranolides: Synthesis of Furanoheliangolides and Cadinanes from Nobilin

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…89 with an EC50 of 0.46 M and a similar SI of 2.4. 94 A related natural product deoxyelephantopin (46), was identified through a bioassay-guided isolation from the tropical plant species…”

Section: Indole Alkaloidsmentioning

confidence: 99%

Active Natural Product Scaffolds against Trypanosomatid Parasites: A Review

Cockram

Smith

2018

J. Nat. Prod.

View full text Add to dashboard Cite

Neglected tropical diseases caused by trypanosomatid parasites are a continuing and escalating problem, which devastate the less economically developed cultures in countries in which they are endemic by impairing both human and animal health. Current drugs for these diseases are regarded as out-of-date, expensive, with unacceptable side-effects and mounting parasite resistance, meaning there is an urgent need for new therapeutics. Natural products have long been a source of potent, structurally diverse bioactive molecules. Herein are reviewed natural products with reported trypanocidal activity, which have been clustered based on core structural similarities, to aid the future discovery of new trypanocidal core motifs with potential routes to synthetically accessible natural product cores suggested.in both the New and Old Worlds, and these include L. amazonensis, L. major, L. infantum and L. donovani. The disease is transmitted via the bite of the female phlebotomine sand fly vector, with an estimated 300,000 new infections each year and over 1 billion people living in areas at risk, primarily throughout the tropics and subtropics. 10

show abstract

“…This compound exhibited significant trypanocidal activity against T. b. rhodesiense (strain STIB 900), with an IC 50 value of 0.024 µg/mL and a CC 50 value (L-cell) of 1.41 µg/mL (SI = 64.5)[58].Nobilin is a natural heliangolide type STL isolated from the flowers of Anthemis nobilis (Asteraceae). The transannular cyclization of nobilin in acidic conditions has been carried out by De Mieri et al[59]. The in vitro anti-trypanosomal activity of the obtained derivatives against T. b. rhodesiense bloodstream forms was evaluated and compared with nobilin (IC 50 = 3.19 μM).…”

mentioning

confidence: 99%

Natural Sesquiterpene Lactones as Potential Trypanocidal Therapeutic Agents: A Review

Muschietti

Ulloa

2016

Natural Product Communications

View full text Add to dashboard Cite

Chagas' disease and Human African Trypanosomiasis are parasitic diseases that remain major health problems, mainly among the poorest and the most marginalized communities from Latin America and Africa. The scarcity of effective chemotherapy, due to the low investment in the research and development (R&D) of new drugs, together with a high incidence of side effects, and the emergence of drug resistance phenomena emphasize the urgent need for new prophylactic and therapeutic agents. Over the ages, humans have employed natural products to treat a wide spectrum of diseases. Recently, the pharmaceutical industry has focused on plant research and a large body of evidence has been collected to demonstrate the immense potential of medicinal plants as a source of bioactive compounds and lead molecules. In the field of parasitic diseases, drug development from plants has been successful for the sesquiterpene lactone (STL) artemisinin, which is employed as an antimalarial agent. STLs are a large group of naturally occurring terpenoids derived from plants that mostly belong to the Asteraceae family which exhibit a variety of skeletal arrangements and are the largest and most diverse category of natural products with an αmethylene-λ-lactone motif. STLs display a broad spectrum of biological activities such as antitumor, cytotoxic, antibacterial, anthelmintic, uterus contracting, antimalarial, neurotoxic, antiprotozoal and allergic (contact dermatitis) activities. In this context, the purpose of the present review is to provide an overview of the trypanocidal activity reported for STLs against Trypanosoma cruzi and T. brucei rhodesiense over the period 1993-2015.

show abstract

Anti-trypanosomal cadinanes synthesized by transannular cyclization of the natural sesquiterpene lactone nobilin

Cited by 6 publications

References 24 publications

Acid-Induced Rearrangement of Epoxygermacranolides: Synthesis of Furanoheliangolides and Cadinanes from Nobilin

Acid-Induced Rearrangement of Epoxygermacranolides: Synthesis of Furanoheliangolides and Cadinanes from Nobilin

Active Natural Product Scaffolds against Trypanosomatid Parasites: A Review

Natural Sesquiterpene Lactones as Potential Trypanocidal Therapeutic Agents: A Review

Contact Info

Product

Resources

About