Inhibition of Quorum Sensing by Drimane Lactones From Chilean Flora

Carcamo, Gerardo; Silva, Mario; Becerra, José; Urrutia, Homero; Sossa, Katherine; Paz, Cristian

doi:10.4067/s0717-97072014000300021

Cited by 16 publications

(8 citation statements)

References 6 publications

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“…It is present at all social and religious meetings, called “guillatún” and “machitún”, where the healer, or “machi”, uses Canelo leaves or sap as medicine. Among the three products of focus here, drimane sesquiterpenoids stand out as secondary metabolites withpotent fungicidal, anti-feeding and insecticidal activities, and drimane sesquiterpene lactones have demonstrated activity on bacterial quorum sensing [ 17 , 18 ]. P. Mitiqui (Lindl) (Asteraceae, Compositae) is another endemic plant of the Central Zone of Chile.…”

Section: Introductionmentioning

confidence: 99%

TrypanocidalActivity of Natural Sesquiterpenoids Involves Mitochondrial Dysfunction, ROS Production and Autophagic Phenotype in Trypanosoma cruzi

et al. 2018

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Chagas disease is a neglected tropical disease that is caused by the protozoan Trypanosoma cruzi and represents a serious health problem, especially in Latin America. The clinical treatment of Chagas disease is based on two nitroderivatives that present severe side effects and important limitations. In folk medicine, natural products, including sesquiterpenoids, have been employed for the treatment of different parasitic diseases. In this study, the trypanocidal activity of compounds isolated from the Chilean plants Drimys winteri, Podanthus mitiqui and Maytenus boaria on three T. cruzi evolutive forms (epimastigote, trypomastigote and amastigote) was evaluated. Total extracts and seven isolated sesquiterpenoids were assayed on trypomastigotes and epimastigotes. Polygodial (Pgd) from D. winteri, total extract from P. mitiqui (PmTE) and the germacrane erioflorin (Efr) from P. mitiqui were the most bioactive substances. Pgd, Efr and PmTE also presented strong effects on intracellular amastigotes and low host toxicity. Many ultrastructural effects of these substances, including reservosome disruption, cytosolic vacuolization, autophagic phenotype and mitochondrial swelling (in the case of Pgd), were observed. Flow cytometric analysis demonstrated a reduction in mitochondrial membrane potential in treated epimastigotes and an increase in ROS production and high plasma membrane permeability after treatment with Pgd. The promising trypanocidal activity of these natural sesquiterpenoids may be a good starting point for the development of alternative treatmentsforChagas disease.

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Section: Introductionmentioning

confidence: 99%

TrypanocidalActivity of Natural Sesquiterpenoids Involves Mitochondrial Dysfunction, ROS Production and Autophagic Phenotype in Trypanosoma cruzi

et al. 2018

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“…Also, polygodial (01-100 µM) inhibited the rhythmic spontaneous contractions of the rat portal vein (Emax by 75 ± 2%.) These results strongly suggest that the vasorelaxant actions produced by polygodial in rat portal vein are associated with inhibition of calcium influx through voltage-sensitive channels and interaction with protein kinase Cdependent mechanisms (Cárcamo et al, 2014).…”

Section: Cardiovascular Effectsmentioning

confidence: 70%

“…Cinnamolide and valdiviolide are αβ unsaturated lactones with the carbonyl in position 12 of the drimane skeleton, whereas drimenin, isodrimenin and isodrimeninol have the carbonyl group at position 11 and are not active. This relationship between structure and activity shows the high specificity of the QS system (Cárcamo et al, 2014).…”

Section: Quorum-sensing Inhibitionmentioning

confidence: 85%

Phytochemistry and biological properties of Drimys winteriJR et G. Forster var chilensis(DC) A.

Muñoz¹,

Tapia²,

Nevermann³

et al. 2021

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Drimys winteri JR et G. Forster var chilensis (DC) A. is a tree native to central and southern Chile. Also it found in part of Argentina. It is abundant in wet swampy localities from sea level to an altitude of 1700 m. This tree is sacred for the Mapuche culture; it is used in folk medicine in such as inflammatory and painful processes. Phytochemical studies have demonstrated that this plant contains mainly sesquiterpenes of the drimane type, flavonoids, essential oils, phytosterols and some lignans. These drimanes have attracted interest because of their antifeedant, plant growth regulation, cytotoxic, antimicrobial and insecticidal properties. The objective of this review is to establish clearly the phytochemistry and biological activity of Drimys winteri JR et G. Forster var chilensis (DC) A. Articles based on other varieties are not considered.

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“…The 1 H NMR (Table S1, Supporting Information) and 13 C NMR (Table S2, Supporting Information) results are in excellent agreement with previous data. 11 ,12 The chemical characterization of drimane sesquiterpenoids coincides with that obtained by X-ray studies, 13−15 where a basic structural framework is shown: a trans-decalin moiety with a Δ 7 (8) double bond, giving a twisted chair conformation at the second ring and conferring a planar C-7−C-8−C-12 dihedral angle of 126.7°for dendocarbin A.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Drimane Sesquiterpenoids Noncompetitively Inhibit Human α4β2 Nicotinic Acetylcholine Receptors with Higher Potency Compared to Human α3β4 and α7 Subtypes

et al. 2018

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The drimane sesquiterpenoids drimenin, cinnamolide, dendocarbin A, and polygodial were purified from the Canelo tree ( Drimys winteri) and chemically characterized by spectroscopic methods. The pharmacological activity of these natural compounds were determined on hα4β2, hα3β4, and hα7 nicotinic acetylcholine receptors (AChRs) by Ca influx measurements. The results established that drimane sesquiterpenoids inhibit AChRs with the following selectivity: hα4β2 > hα3β4 > hα7. In the case of hα4β2 AChRs, the following potency rank order was determined (IC's in μM): drimenin (0.97 ± 0.35) > cinnamolide (1.57 ± 0.36) > polygodial (62.5 ± 19.9) ≫ dendocarbin A (no activity). To determine putative structural features underlying the differences in inhibitory potency at hα4β2 AChRs, additional structure-activity relationship and molecular docking experiments were performed. The Ca influx and structural results supported a noncompetitive mechanism of inhibition, where drimenin interacted with luminal and nonluminal (TMD-β2 intrasubunit) sites. The structure-activity relationship results, i.e., the lower the ligand polarity, the higher the inhibitory potency, supported the nonluminal interaction. Ligand binding to both sites might inhibit the hα4β2 AChR by a cooperative mechanism, as shown experimentally ( n > 1). Drimenin could be used as a molecular scaffold for the development of more potent inhibitors with higher selectivity for the hα4β2 AChR.

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Inhibition of Quorum Sensing by Drimane Lactones From Chilean Flora

Cited by 16 publications

References 6 publications

TrypanocidalActivity of Natural Sesquiterpenoids Involves Mitochondrial Dysfunction, ROS Production and Autophagic Phenotype in Trypanosoma cruzi

TrypanocidalActivity of Natural Sesquiterpenoids Involves Mitochondrial Dysfunction, ROS Production and Autophagic Phenotype in Trypanosoma cruzi

Phytochemistry and biological properties of Drimys winteriJR et G. Forster var chilensis(DC) A.

Drimane Sesquiterpenoids Noncompetitively Inhibit Human α4β2 Nicotinic Acetylcholine Receptors with Higher Potency Compared to Human α3β4 and α7 Subtypes

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