Synthesis of Small Combinatorial Libraries of Natural Products: Identification and Quantification of New Long‐chain 3‐Methyl‐2‐alkanones from the Root Essential Oil of <i>Inula helenium</i> L. (Asteraceae)

Radulović, Niko S.; Denić, Marija S.; Stojanović-Radić, Zorica

doi:10.1002/pca.2466

Cited by 15 publications

(16 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although meager research has been conducted in IH, the findings presented here are in alignment with existing researchers who have reported its capacity to attenuate iNOS/NO2-, COX-2/PGE2, HMGB1 release and NF-κB in LPS-activated RAW 264.7 cells or phorbol activated T cells [45–48]. Interestingly, although we did not find IH to have significant antimicrobial effects on E.coli 0157:H7 (1x10 6 CFU/mL) at the low concentrations criteria used in this study, others have reported its capacity to destroy invasive pathogens such as Staphylococcus aureus /methicillin-resistant (MRSA) gram-positive bacteria, yeasts parasites and Mycobacterium tuberculosis [42, 49–53]. These studies suggest IH as being somewhat promising for attenuating inflammation arising from diverse infective or inflammatory insults.…”

Section: Discussionmentioning

confidence: 55%

Natural product HTP screening for antibacterial (E.coli 0157:H7) and anti-inflammatory agents in (LPS from E. coli O111:B4) activated macrophages and microglial cells; focus on sepsis

Mazzio

Bauer

et al. 2016

BMC Complement Altern Med

View full text Add to dashboard Cite

BackgroundAcute systemic inflammatory response syndrome arising from infection can lead to multiple organ failure and death, with greater susceptibility occurring in immunocompromised individuals. Moreover, sub-acute chronic inflammation is a contributor to the pathology of diverse degenerative diseases (Parkinson’s disease, Alzheimer’s disease and arthritis). Given the known limitations in Western medicine to treat a broad range of inflammatory related illness as well as the emergence of antibiotic resistance, there is a renewed interest in complementary and alternative medicines (CAMs) to achieve these means.MethodsA high throughput (HTP) screening of >1400 commonly sold natural products (bulk herbs, cooking spices, teas, leaves, supplement components, nutraceutical food components, fruit and vegetables, rinds, seeds, polyphenolics etc.) was conducted to elucidate anti-inflammatory substances in lipopolysaccharide (LPS) (E. coli serotype O111:B4) monocytes: RAW 264.7 macrophages [peripheral], BV-2 microglia [brain]) relative to hydrocortisone, dexamethasone and L-N6-(1Iminoethyl)lysine (L-NIL). HTP evaluation was also carried out for lethal kill curves against E.coli 0157:H7 1x106 CFU/mL relative to penicillin. Validation studies were performed to assess cytokine profiling using antibody arrays. Findings were corroborated by independent ELISAs and NO2–/iNOS expression quantified using the Griess Reagent and immunocytochemistry, respectively. For robust screening, we developed an in-vitro efficacy paradigm to ensure anti-inflammatory parameters were observed independent of cytotoxicity. This caution was taken given that many plants exert tumoricidal and anti-inflammatory effects at close range through similar signaling pathways, which could lead to false positives.ResultsThe data show that activated BV-2 microglia cells (+ LPS 1μg/ml) release >10-fold greater IL-6, MIP1/2, RANTES and nitric oxide (NO2–), where RAW 264.7 macrophages (+ LPS 1μg/ml) produced > 10-fold rise in sTNFR2, MCP-1, IL-6, GCSF, RANTES and NO2–. Data validation studies establish hydrocortisone and dexamethasone as suppressing multiple pro-inflammatory processes, where L-NIL suppressed NO2–, but had no effect on iNOS expression or IL-6. The screening results demonstrate relative few valid hits with anti-inflammatory effects at < 250μg/ml for the following: Bay Leaf (Laurus nobilis), Elecampagne Root (Inula helenium), Tansy (Tanacetum vulgare),Yerba (Eriodictyon californicum) and Centipeda (Centipeda minima), Ashwagandha (Withania somnifera), Feverfew (Tanacetum parthenium), Rosemary (Rosmarinus officinalis), Turmeric Root (Curcuma Longa), Osha Root (Ligusticum porteri), Green Tea (Camellia sinensis) and constituents: cardamonin, apigenin, quercetin, biochanin A, eupatorin, (-)-epigallocatechin gallate (EGCG) and butein. Natural products lethal against [E. coli 0157:H7] where the LC50 < 100 μg/ml included bioactive silver hydrosol-Argentyn 23, green tea (its constituents EGCG > Polyphenon 60 > (-)-Gallocatechin > Epicatechin > (+)-Catechin), G...

show abstract

Section: Discussionmentioning

confidence: 55%

Natural product HTP screening for antibacterial (E.coli 0157:H7) and anti-inflammatory agents in (LPS from E. coli O111:B4) activated macrophages and microglial cells; focus on sepsis

Mazzio

Bauer

et al. 2016

BMC Complement Altern Med

View full text Add to dashboard Cite

show abstract

“…SLA enables a simultaneous identification of not only specific, new compounds, but of a series of its homologs/analogs (Figure ). This approach was recently successfully applied in the analysis of different essential oil samples …”

Section: Introductionmentioning

confidence: 99%

“…Although previous applications of SLA were mainly targeted ones (libraries of compounds were designed to resolve problems related to a single EO sample), the possible benefits of a more general employment of SLA in EO chemistry was already recognized . In this more universal approach, chemical profiles of previously studied essential oils are used as ‘sources of the likely SL‐parent‐structures’ (SL‐synthetic library), Figure , route c, step 1.…”

Section: Introductionmentioning

confidence: 99%

Essential‐oil inspired synthetic libraries: synthesis, spectral and gas‐chromatographic properties of new fenchyl esters

Blagojević

Pešić

Radulović

2017

Flavour & Fragrance J

Self Cite

View full text Add to dashboard Cite

Herein, the design, synthesis, and gas‐chromatographic and spectral characterization of a library of endo‐ and exo‐fenchyl esters (formate, acetate, propanoate, butanoate, isobutanoate, pentanoate, isopentanoate, 2‐methylbutanoate, hexanoate, heptanoate, octanoate, nonanoate, tiglate, angelate, senecioate and benzoate; 32 compounds in total) were described. 1D‐ and 2D–NMR experiments combined with 1H iterative full spin analysis and GIAO (gauge invariant atomic orbitals) computation of NMR chemical shifts and coupling constants for DFT‐calculated minimum energy conformations enabled a complete 1H–NMR assignment of the higher‐order signals of the fenchyl‐core protons. Library members, derivatives of a well‐known monoterpenol of economical importance, often encountered in essential oils (EOs), might potentially represent new (up to now undiscovered), or be classified as rare, natural products. The data summarized in this work should facilitate future EO analyses, especially those studies dealing with minor constituents. The benefits of the usage of (untargeted) metabolome‐inspired synthetic libraries in the analysis of EOs were discussed.

show abstract

“…The resolution of accidently overlapped signals from two or more different molecules could be a plausible outcome of a gradual addition of a LSR directly to the mixture since a distinct conduct of these signals is expected due to molecular differences (differing spatial relationship with the LSR complexing functional group and its identity), competitive complexation (differing stabilities of the LSR complexes of different mixture constituents) and shiing of the complexation equilibrium by different amounts of the individual constituents. 19,20 The identity of the 3-methyl-2-alkanones was conrmed by a synthetic approach based on the creation of a combinatorial library of such compounds since the amount and complexity of the fraction did not permit further chromatographic separation. [15][16][17] Also, the presence of LSR, that are paramagnetic in nature, should result in the increased 13 C NMR sensitivity and shorten the time needed to acquire good quality spectra even for samples available in low amount.…”

Section: Introductionmentioning

confidence: 99%

“…[15][16][17] Also, the presence of LSR, that are paramagnetic in nature, should result in the increased 13 C NMR sensitivity and shorten the time needed to acquire good quality spectra even for samples available in low amount. 20 In order to identify this sesquiterpene aldehyde, a larger quantity of the essential oil was fractionated by chromatography on SiO 2 . 1 The original TIC chromatogram of a GC-MS run of a fraction (5% diethyl ether in hexane) of I. helenium root essential oil showing peaks with retention indices (blue colored) corresponding to a series of 3-methyl-2-alkanones and an unidentified sesquiterpene aldehyde (green colored) and the mass spectrum of the aldehyde.…”

Section: Introductionmentioning

confidence: 99%

Lanthanide-induced shift reagents enable the structural elucidation of natural products in inseparable complex mixtures – the case of elemenal from Inula helenium L. (Asteraceae)

Genčić

Radulović

2015

RSC Adv.

Self Cite

View full text Add to dashboard Cite

The use of lanthanide complexes for resolving intricate NMR signals and, in the case of chiral ligands, for determining enantiomeric excess has progressively decreased in the last 30 years. Recently, a sesquiterpene aldehyde from Inula helenium with a possible potent antistaphylococcal activity remained unidentified due to the impossibility of separating the compound from its complex matrix available in very low amounts (ca. 5 mg). Detailed analyses of 1D and 2D NMR spectra of this original complex sample allowed access to a very limited amount of structural data for the unknown aldehyde. We decided to investigate the potential usefulness of lanthanide-induced shift reagents for the resolution and assigning of overlapped 1 H NMR signals originating from different components of this complex mixture (i.e. for a qualitative analysis). The incremental addition of tris (6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionato)europium(III) (Eu(fod) 3 ) led to a simplification of the NMR spectra in terms of signal overlap and removal of chemical shift degeneracy, allowing the mining of crucial data from the shifted NMR spectra. 2D NMR spectra ( 1 H-1 H-COSY, NOESY, HSQC and HMBC) of the sample mixed with Eu(fod) 3 proved to be particularly valuable in this respect. The obtained additional information revealed that the compound in question was a rare sesquiterpeneelemenal (elema-1,3,11(13)-trien-12al). Therefore, herein we report on a new chromatography-free methodology that could be of value in structure elucidation of unknown compounds even if they are not available in a pure state. 18533014; Tel: +381 18533015 † Electronic supplementary information (ESI) available: A comparison of experimental and simulated 1 H NMR spectra of elemenal (the second order vinyl group spin system). Results of the conformational analysis of elemenal-Eu(fod) 3 complex obtained using the lanthanide probe method. See Fig. 6 The chemical shift vs. the ratio of the shift reagent and elemenal plots obtained from the incremental addition of Eu(fod) 3 to elemenal for: (a) the protons closest to the coordination site, (b) the remaining olefinic protons and (c) for the protons that resonated at the high field region.This journal is

show abstract

Synthesis of Small Combinatorial Libraries of Natural Products: Identification and Quantification of New Long‐chain 3‐Methyl‐2‐alkanones from the Root Essential Oil of Inula helenium L. (Asteraceae)

Cited by 15 publications

References 17 publications

Natural product HTP screening for antibacterial (E.coli 0157:H7) and anti-inflammatory agents in (LPS from E. coli O111:B4) activated macrophages and microglial cells; focus on sepsis

Natural product HTP screening for antibacterial (E.coli 0157:H7) and anti-inflammatory agents in (LPS from E. coli O111:B4) activated macrophages and microglial cells; focus on sepsis

Essential‐oil inspired synthetic libraries: synthesis, spectral and gas‐chromatographic properties of new fenchyl esters

Lanthanide-induced shift reagents enable the structural elucidation of natural products in inseparable complex mixtures – the case of elemenal from Inula helenium L. (Asteraceae)

Contact Info

Product

Resources

About