Activity of Compounds from Temperate Propolis against Trypanosoma brucei and Leishmania mexicana

Ethanolic extracts of samples of temperate zone propolis, four from the UK and one from Poland, were tested against three Trypanosoma brucei strains and displayed EC50 values < 20 µg/mL. The extracts were fractionated, from which 12 compounds and one two-component mixture were isolated, and characterized by NMR and high-resolution mass spectrometry, as 3-acetoxypinobanksin, tectochrysin, kaempferol, pinocembrin, 4′-methoxykaempferol, galangin, chrysin, apigenin, pinostrobin, cinnamic acid, coumaric acid, cinnamyl ester/coumaric acid benzyl ester (mixture), 4′,7-dimethoxykaempferol, and naringenin 4′,7-dimethyl ether. The isolated compounds were tested against drug-sensitive and drug-resistant strains of T. brucei and Leishmania mexicana, with the highest activities ≤ 15 µM. The most active compounds against T. brucei were naringenin 4′,7 dimethyl ether and 4′methoxy kaempferol with activity of 15–20 µM against the three T. brucei strains. The most active compounds against L. mexicana were 4′,7-dimethoxykaempferol and the coumaric acid ester mixture, with EC50 values of 12.9 ± 3.7 µM and 13.1 ± 1.0 µM. No loss of activity was found with the diamidine- and arsenical-resistant or phenanthridine-resistant T. brucei strains, or the miltefosine-resistant L. mexicana strain; no clear structure activity relationship was observed for the isolated compounds. Temperate propolis yields multiple compounds with anti-kinetoplastid activity.

Download Full-text

Cinnamoylphenethyl Amides from Polygonum hyrcanicum Possess Anti-Trypanosomal Activity

Natural Product Communications ◽

10.1177/1934578x1200700616 ◽

2012 ◽

Vol 7 (6) ◽

pp. 1934578X1200700 ◽

Cited By ~ 4

Author(s):

Fahimeh Moradi-Afrapoli ◽

Nargues Yassa ◽

Stefanie Zimmermann ◽

Soodabeh Saeidnia ◽

Abbas Hadjiakhoondi ◽

...

Keyword(s):

Ferulic Acid ◽

Trypanosoma Brucei ◽

Methanolic Extract ◽

Coumaric Acid ◽

Trypanosoma Brucei Rhodesiense ◽

Active Compounds ◽

Active Constituents ◽

L6 Cells ◽

Aerial Parts ◽

Bioassay Guided Fractionation

A methanolic extract from aerial parts of Polygonum hyrcanicum (Polygonaceae) showed high activity against Trypanosoma brucei rhodesiense (IC50=3.7 μg/mL). Bioassay-guided fractionation of the extract resulted in isolation of cinnamoylphenethyl amides, including N-trans-caffeoyltyramine (1), N-trans-p-coumaroyltyramine (7), and N-trans-feruloyltyramine (8) as the main active constituents (IC50s ranging from 2.2 to 13.3 μM). Some structurally related, but less active compounds, such as cannabisin B (2), tyrosol (3), p-coumaric acid (4), ferulic acid (5), and N-cis-feruloyltyramine (6) were also identified, along with N-trans-3,4-dimethoxycinnamoyldopamine (9). Cytotoxicity of the active compounds in L6 cells was determined, and selectivity indices (SI) of 7.9 to 33.4 were calculated.

Download Full-text

Screening of some Asteraceae to discover new active compounds against Trypanosoma brucei by metabolite profiling and PLS analysis

Planta Medica ◽

10.1055/s-0033-1351830 ◽

2013 ◽

Vol 79 (13) ◽

Cited By ~ 1

Author(s):

MS Nogueira ◽

FB da Costa ◽

MA Magenta ◽

M Kaiser ◽

R Brun ◽

...

Keyword(s):

Trypanosoma Brucei ◽

Metabolite Profiling ◽

Active Compounds ◽

Pls Analysis

Download Full-text

Exploring the Active Compounds of Traditional Mongolian Medicine Agsirga in Intervention of Novel Coronavirus (2019-nCoV) Based on HPLC-Q-Exactive-MS/MS and Molecular Docking Method

10.26434/chemrxiv.11955273 ◽

2020 ◽

Author(s):

Jie Cheng ◽

Yuchen Tang ◽

Baoquan Bao ◽

Ping Zhang

Keyword(s):

Mass Spectrometry ◽

Molecular Docking ◽

High Resolution ◽

Mass Spectra ◽

High Resolution Mass Spectrometry ◽

Structural Formula ◽

Active Compounds ◽

High Resolution Mass ◽

Q Exactive ◽

Resolution Mass

<a></a><a></a><a></a><a>Objective</a>: To screen all compounds of Agsirga based on the HPLC-Q-Exactive high-resolution mass spectrometry and find potential inhibitors that can respond to 2019-nCoV from active compounds of Agsirga by molecular docking technology. Methods: HPLC-Q-Exactive high-resolution mass spectrometry was adopted to identify the complex components of Mongolian medicine Agsirga, and separated by the high-resolution mass spectrometry Q-Exactive detector. Then the Orbitrap detector was used in tandem high-resolution mass spectrometry, and the related molecular and structural formula were found by using the chemsipider database and related literature, combined with precise molecular formulas (errors ≤ 5 × 10−6) , retention time, primary mass spectra, and secondary mass spectra information, The fragmentation regularities of mass spectra of these compounds were deduced. Taking ACE2 as the receptor and deduced compounds as the ligand, all of them were pretreated by discover studio, autodock and Chem3D. The molecular docking between the active ingredients and the target protein was studied by using AutoDock molecular docking software. The interaction between ligand and receptor is applied to provide a choice for screening anti-2019-nCoV drugs. Result: Based on the fragmentation patterns of the reference compounds and consulting literature, a total of 96 major alkaloids and stilbenes were screened and identified in Agsirga by the HPLC-Q-Exactive-MS/MS method. Combining with molecular docking, a conclusion was got that there are potential active substances in Mongolian medicine Agsirga which can block the binding of ACE2 and 2019-nCoV at the molecular level.

Download Full-text

Anti-MRSA Constituents from Ruta chalepensis (Rutaceae) Grown in Iraq, and In Silico Studies on Two of Most Active Compounds, Chalepensin and 6-Hydroxy-rutin 3′,7-Dimethyl ether

Molecules ◽

10.3390/molecules26041114 ◽

2021 ◽

Vol 26 (4) ◽

pp. 1114 ◽

Cited By ~ 1

Author(s):

Shaymaa Al-Majmaie ◽

Lutfun Nahar ◽

M. Mukhlesur Rahman ◽

Sushmita Nath ◽

Priyanka Saha ◽

...

Keyword(s):

Dimethyl Ether ◽

In Silico ◽

Efflux Pump ◽

Perennial Herb ◽

Flavonoid Glycosides ◽

Cinnamic Acid Derivative ◽

Active Compounds ◽

Ruta Chalepensis ◽

In Silico Studies ◽

Mrsa Strains

Ruta chalepensis L. (Rutaceae), a perennial herb with wild and cultivated habitats, is well known for its traditional uses as an anti-inflammatory, analgesic, antipyretic agent, and in the treatment of rheumatism, nerve diseases, neuralgia, dropsy, convulsions and mental disorders. The antimicrobial activities of the crude extracts from the fruits, leaves, stem and roots of R. chalepensis were initially evaluated against two Gram-positive and two Gram-negative bacterial strains and a strain of the fungus Candida albicans. Phytochemical investigation afforded 19 compounds, including alkaloids, coumarins, flavonoid glycosides, a cinnamic acid derivative and a long-chain alkane. These compounds were tested against a panel of methicillin-resistant Staphylococcus aureus (MRSA) strains, i.e., ATCC 25923, SA-1199B, XU212, MRSA-274819 and EMRSA-15. The MIC values of the active compounds, chalepin (9), chalepensin (10), rutamarin (11), rutin 3′-methyl ether (14), rutin 7,4′-dimethyl ether (15), 6-hydroxy-rutin 3′,7-dimethyl ether (16) and arborinine (18) were in the range of 32–128 µg/mL against the tested MRSA strains. Compounds 10 and 16 were the most active compounds from R. chalepensis, and were active against four out of six tested MRSA strains, and in silico studies were performed on these compounds. The anti-MRSA activity of compound 16 was comparable to that of the positive control norfloxacin (MICs 32 vs 16 μg/mL, respectively) against the MRSA strain XU212, which is a Kuwaiti hospital isolate that possesses the TetK tetracycline efflux pump. This is the first report on the anti-MRSA property of compounds isolated from R. chalepensis and relevant in silico studies on the most active compounds.

Download Full-text

Structural Elucidation and Cytotoxicity of a New 17-Membered Ring Lactone from Algerian Eryngium campestre

Molecules ◽

10.3390/molecules23123250 ◽

2018 ◽

Vol 23 (12) ◽

pp. 3250 ◽

Cited By ~ 3

Author(s):

Ali Medbouhi ◽

Aura Tintaru ◽

Claire Beaufay ◽

Jean-Valère Naubron ◽

Nassim Djabou ◽

...

Keyword(s):

Chemical Composition ◽

Trypanosoma Brucei ◽

Crude Extract ◽

Membered Ring ◽

Leishmania Mexicana ◽

Similar Concentration ◽

Trypanosoma Brucei Brucei ◽

Aerial Parts ◽

Germacrene D ◽

Low Activity

The chemical composition of a hexanic extract of Eryngium campestre, obtained from its aerial parts, was investigated by GC-FID, GC/MS, HRMS, NMR and VCD analyses. The main compounds were germacrene D (23.6%), eudesma-4(15)-7-dien-1-β-ol (8.2%) and falcarindiol (9.4%), which are associated with a new uncommon and naturally found 17-membered ring lactone. This 17-membered ring features conjugated acetylenic bonds, named campestrolide (23.0%). The crude extract showed moderate antitrypanosomal (Trypanosoma brucei brucei), antileishmanial (Leishmania mexicana mexicana) and anticancer (cancerous macrophage-like murine cells) activities, and also displayed cytotoxicity, (human normal fibroblasts) in similar concentration ranges (IC50 = 3.0, 3.9, 4.0 and 4.4 µg/mL respectively). Likewise, campestrolide displayed low activity on all tested cells (IC50: 12.5–19.5 µM) except on Trypanosoma, on which it was very active and moderately selective (IC50 = 2.2 µM. SI= 8.9). In conclusion, the new compound that has been described, displaying a singular structure, possesses interesting antitrypanosomal activity that should be further investigated and improved.

Download Full-text

A toolkit enabling efficient, scalable and reproducible gene tagging in trypanosomatids

Open Biology ◽

10.1098/rsob.140197 ◽

2015 ◽

Vol 5 (1) ◽

pp. 140197 ◽

Cited By ~ 97

Author(s):

Samuel Dean ◽

Jack Sunter ◽

Richard J. Wheeler ◽

Ian Hodkinson ◽

Eva Gluenz ◽

...

Keyword(s):

Trypanosoma Brucei ◽

Large Datasets ◽

Gene Tagging ◽

Deletion Mutants ◽

Whole Genome ◽

Leishmania Mexicana ◽

Protein Coding ◽

Achievable Goal ◽

Endogenous Loci ◽

Pcr Conditions

One of the first steps in understanding a protein's function is to determine its localization; however, the methods for localizing proteins in some systems have not kept pace with the developments in other fields, creating a bottleneck in the analysis of the large datasets that are generated in the post-genomic era. To address this, we developed tools for tagging proteins in trypanosomatids. We made a plasmid that, when coupled with long primer PCR, can be used to produce transgenes at their endogenous loci encoding proteins tagged at either terminus or within the protein coding sequence. This system can also be used to generate deletion mutants to investigate the function of different protein domains. We show that the length of homology required for successful integration precluded long primer PCR tagging in Leishmania mexicana . Hence, we developed plasmids and a fusion PCR approach to create gene tagging amplicons with sufficiently long homologous regions for targeted integration, suitable for use in trypanosomatids with less efficient homologous recombination than Trypanosoma brucei . Importantly, we have automated the primer design, developed universal PCR conditions and optimized the workflow to make this system reliable, efficient and scalable such that whole genome tagging is now an achievable goal.

Download Full-text

Glucose-6-Phosphate Dehydrogenase of Trypanosomatids: Characterization, Target Validation, and Drug Discovery

Molecular Biology International ◽

10.4061/2011/135701 ◽

2011 ◽

Vol 2011 ◽

pp. 1-10 ◽

Cited By ~ 10

Author(s):

Shreedhara Gupta ◽

Mariana Igoillo-Esteve ◽

Paul A. M. Michels ◽

Artur T. Cordeiro

Keyword(s):

Oxidative Stress ◽

Enzyme Activity ◽

Trypanosoma Brucei ◽

Redox State ◽

Chemotherapeutic Agents ◽

Dependent Manner ◽

Target Validation ◽

Leishmania Mexicana ◽

State Dependent ◽

Glucose 6 Phosphate Dehydrogenase

In trypanosomatids, glucose-6-phosphate dehydrogenase (G6PDH), the first enzyme of the pentosephosphate pathway, is essential for the defense of the parasite against oxidative stress. Trypanosoma brucei, Trypanosoma cruzi, and Leishmania mexicana G6PDHs have been characterized. The parasites' G6PDHs contain a unique 37 amino acid long N-terminal extension that in T. cruzi seems to regulate the enzyme activity in a redox-state-dependent manner. T. brucei and T. cruzi G6PDHs, but not their Leishmania spp. counterpart, are inhibited, in an uncompetitive way, by steroids such as dehydroepiandrosterone and derivatives. The Trypanosoma enzymes are more susceptible to inhibition by these compounds than the human G6PDH. The steroids also effectively kill cultured trypanosomes but not Leishmania and are presently considered as promising leads for the development of new parasite-selective chemotherapeutic agents.

Download Full-text

Acidic Growth Inhibitors From Peach Buds

Functional Plant Biology ◽

10.1071/pp9750105 ◽

1975 ◽

Vol 2 (2) ◽

pp. 105 ◽

Cited By ~ 2

Author(s):

S Altree-Williams ◽

MEH Howden ◽

JT Keegan ◽

HDR Malcolm ◽

SG Wyllie

Keyword(s):

High Resolution Mass Spectrometry ◽

Gas Liquid Chromatography ◽

Wheat Coleoptile ◽

Growth Inhibitors ◽

Coumaric Acid ◽

Flower Buds ◽

Growth Activity ◽

Peach Trees ◽

Plant Growth Inhibitors ◽

Resolution Mass

Plant growth inhibitors identified in acidic extracts of flower buds from mature peach trees were p-coumaric acid, feruIic acid, an isomeric hydroxymethoxycinnamic acid, a dihydroxycinnamic acid having the properties of 3,5-dihydroxycinnamic acid, and benzoic acid. The inhibitors were isolated by preparative gas-liquid chromatography, tested for growth activity on the wheat coleoptile straight-growth bioassay, and identified by high-resolution mass spectrometry.

Download Full-text