Five putrescine and spermidine derivatives (1-5) together with five rotenoids (6-10) were isolated from a methanolic extract of the flowers of A. fruticosa that displayed promising inhibition of 76.0 ± 1.9% for AChE and 90.0 ± 4.0% for BuChE at a concentration of 1 mg/mL. Although the anticholinesterase activities of the isolated compounds did not reach that of galantamine, molecular docking revealed that all-trans-tri-p-coumaroylspermidine and trans-trans-cis-tri-p-coumaroylspermidine showed binding poses mimicking the known inhibitor galantamine and thus could serve as model molecules in future searches for new AChE and BuChE inhibitors.
- Publikační typ
- časopisecké články MeSH
Fourteen diterpenes were isolated from methanol extracts of the aerial parts ofColeus comosus,Coleus forsteri "Marginatus", and Plectranthus ciliatus. The compounds belong to the abietane (1-4, 9-11, and 13), ent-clerodane (5-8), and ent-kaurane (14, 15) classes. Three new compounds were isolated from C. comosus, including 3-O-acetylornatin G (2), 3,12-di-O-acetylornatin G (3), ornatin B methyl ester (5), and ornatin F (4), for which we proposed a revised structure. The structures of the compounds were determined by comprehensive spectroscopic data analysis. The isolated diterpenes were examined in silico for their physicochemical and early ADME properties. Their antiproliferative effects were determined in vitro using human breast (MDA-MB-231 and MCF-7), cervical (HeLa), and glioblastoma (U-87 MG) cancer cell lines. The royleanone- and hydroquinone-type abietane diterpenes (9-13)exhibited the most potent antiproliferative activity against all cancer cell lines tested, particularly against glioblastoma cells, with IC50 values ranging from 1.1 to 15.6 μM.
- Publikační typ
- časopisecké články MeSH
Plectranthus (Lamiaceae), which-according to the latest systematic revision-includes three separate genera (Coleus, Plectranthus sensu stricto, and Equilabium), is a genus widely used in traditional medicine-mainly in the treatment of various ailments of the digestive tract, respiratory tract, and skin. Many species of Plectranthus s.l. have been shown to produce phenolic compounds and terpenes. Diterpenes, especially those of the abietane class, are the most studied group of secondary metabolites found in Plectranthus s.l., which is characterized by a significant structural diversity arising from the oxygenation and further rearrangement of the basic tricyclic abietane skeleton to a complete aromatization of the ring system. This review summarizes the known information on abietane diterpenes, showing their structures, sources, and biosynthesis. A classification of these compounds into nine groups, according to the arrangement of their ring C, is used. Royleanones, spirocoleons, and hydroquinones are the largest classes of abietane diterpenes, covering more than 70% of all the compounds reviewed.
- MeSH
- diterpeny abietanové chemie MeSH
- diterpeny chemie MeSH
- fytonutrienty chemie izolace a purifikace farmakologie MeSH
- molekulární struktura MeSH
- Plectranthus chemie MeSH
- rostlinné extrakty chemie izolace a purifikace farmakologie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
Two heretofore uncharacterised abietane diterpenes, sincoetsin C (1) and 3-hydroxyspirocoleon 7-O-β-D-glucoside (4), were isolated from a methanolic extract of Coleus blumei Benth. (Lamiaceae), along with the known compounds, scutellarioidone A (2) and spirocoleon 7-O-β-D-glucoside (3) using chromatographic techniques. Their structures were determined by 1D and 2D nuclear magnetic resonance including HSQC, HMBC, COSY and NOESY experiments, mass spectrometry (HR-MS) and other spectroscopic methods (UV, IR). Their antibacterial activity against the reference strain of methicillin-resistant Staphylococcus aureus subsp. aureus CCM 4750 (MRSA) was evaluated using optical absorption to obtain quantitative information on their growth. All isolated compounds displayed anti-MRSA 4750 activity at the concentration of 512 μg/mL. Sincoetsin C (1) was the abietane diterpene most active against MRSA 4750, with a minimum inhibitory concentration of 128 μg/mL.
- MeSH
- Coleus * chemie MeSH
- diterpeny abietanové izolace a purifikace farmakologie MeSH
- diterpeny * izolace a purifikace farmakologie MeSH
- fytonutrienty izolace a purifikace farmakologie MeSH
- methicilin rezistentní Staphylococcus aureus * účinky léků MeSH
- Staphylococcus účinky léků MeSH
- Publikační typ
- časopisecké články MeSH
Fytochemická analýza methanolického extraktu Helichrysum petiolare Hilliard & B. L. (Asteraceae) prokázala přítomnost sekundárních metabolitů patřících mezi fenylpropanoidy a flavonoidy. Pomocí preparativní HPLC se podařilo vyizolovat pět obsahových látek: kumarin skopolin (1), kyselinu 3-chlorogenovou (2), glukosidicky vázaný derivát kyseliny kávové (3), kyselinu dikafeoylchinovou (5) a flavonoid isokvercitrin (4). V druhu H. petiolare byly tyto sloučeniny identifikovány poprvé. Při testování antibakteriální aktivity bylo zjištěno, že pouze kyselina dikafeoylchinová vykazuje mírnou antibakteriální aktivitu proti Escherichia coli CCM 7929 v koncentraci 512 μg ∙ ml–1.
The phytochemical analysis of a methanolic extract from Helichrysum petiolare Hilliard & B. L. (Asteraceae) confirmed the content of phenylpropanoids and flavonoids. Five secondary metabolites were isolated using preparative HPLC, namely coumarin scopolin (1), 3-chlorogenic acid (2), caffeic acid-hexose derivative (3), dicaffeoylquinic acid (5), and the flavonoid isoquercitrin (4). These compounds were identified from this species for the first time. Only dicaffeoylquinic acid was able to inhibit Escherichia coli CCM 7929 at the concertation of 512 μg ∙ mL–1 in a screening of antibacterial activity.
BACKGROUND: The indole derivatives and the N-phenylpiperazine fragment represent interesting molecular moieties suitable for the research of new potentially biologically active compounds. This study was undertaken to identify if indol-2-carboxylic acid esters containing N-phenylpiperazine moiety possess acetylcholinesterase and butyrylcholinesterase inhibitory activity. MATERIALS AND METHODS: The study dealt with the synthesis of a novel series of analogs of 1H-indole-2- carboxylic acid and 3-methyl-1H-indole-2-carboxylic acid. The structure of the derivatives was represented by the indolylcarbonyloxyaminopropanol skeleton with the attached N-phenylpiperazine or diethylamine moiety, which formed a basic part of the molecule. The final products were synthesized as dihydrochloride salts, fumaric acid salts, and quaternary ammonium salts. The first step of the synthetic pathway led to the preparation of esters of 1H-indole-2-carboxylic acid from the commercially available 1H-indole-2-carboxylic acid. The Fischer indole synthesis was used to synthesize derivatives of 3-methyl-1H-indole-2-carboxylic acid. RESULTS AND DISCUSSION: Final 18 indolylcarbonyloxyaminopropanols in the form of dihydrochlorides, fumarates, and quaternary ammonium salts were prepared using various optimization ways. The very efficient way for the formation of 3-methyl-1H-indole-2-carboxylate (Fischer indole cyclization product) was the one-pot synthesis of phenylhydrazine with methyl 2-oxobutanoate with acetic acid and sulphuric acid as catalysts. CONCLUSION: Most of the derivatives comprised of an attached N-phenylpiperazine group, which formed a basic part of the molecule and in which the phenyl ring was substituted in position C-2 or C-4. The synthesized compounds were subjected to cholinesterase-inhibiting activity evaluation, by modified Ellman method. Quaternary ammonium salt of 1H-indole-2-carboxylic acid which contain N-phenylpiperazine fragment with nitro group in position C-4 (7c) demonstrated the most potent activity against acetylcholinesterase.
- MeSH
- acetylcholinesterasa chemie MeSH
- butyrylcholinesterasa chemie MeSH
- cholinesterasové inhibitory chemická syntéza chemie MeSH
- Electrophorus MeSH
- enzymatické testy MeSH
- estery chemická syntéza chemie MeSH
- indoly chemická syntéza chemie MeSH
- koně MeSH
- piperaziny chemická syntéza chemie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Neurodegenerative diseases in which the decrease of the acetylcholine is observed are growing worldwide. In the present study, a series of new arylaminopropanone derivatives with N-phenylcarbamate moiety (1-16) were prepared as potential acetylcholinesterase and butyrylcholinesterase inhibitors. In vitro enzyme assays were performed; the results are expressed as a percentage of inhibition and the IC50 values. The inhibitory activities were compared with reference drugs galantamine and rivastigmine showing piperidine derivatives (1-3) as the most potent. A possible mechanism of action for these compounds was determined from a molecular modelling study by using combined techniques of docking, molecular dynamics simulations and quantum mechanics calculations.
- MeSH
- aktivace enzymů účinky léků MeSH
- cholinesterasové inhibitory chemická syntéza chemie farmakologie MeSH
- lidé MeSH
- molekulární konformace MeSH
- molekulární modely MeSH
- molekulární struktura MeSH
- propanolaminy chemická syntéza chemie farmakologie MeSH
- simulace molekulární dynamiky MeSH
- simulace molekulového dockingu MeSH
- vazba proteinů MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Tertiary amines 3-(dialkylamino)-2-hydroxypropyl 4-[(alkoxycarbonyl)amino]benzoates and their quaternary ammonium salts were synthesized. The final step of synthesis of quaternary ammonium salts was carried out by microwave-assisted synthesis. Software-calculated data provided the background needed to compare fifteen new resulting compounds by their physicochemical properties. The acid dissociation constant (pKa) and lipophilicity index (log P) of tertiary amines were determined; while quaternary ammonium salts were characterized by software-calculated lipophilicity index and surface tension. Biological evaluation aimed at testing acetylcholinesterase and butyrylcholinesterase-inhibiting activity of synthesized compounds. A possible mechanism of action of these compounds was determined by molecular modelling study using combined techniques of docking; molecular dynamics simulations and quantum mechanics calculations.
- MeSH
- acetylcholinesterasa MeSH
- aktivace enzymů účinky léků MeSH
- benzoáty chemická syntéza chemie farmakologie MeSH
- butyrylcholinesterasa MeSH
- chemické modely MeSH
- cholinesterasové inhibitory chemická syntéza chemie farmakologie MeSH
- kvartérní amoniové sloučeniny chemická syntéza chemie farmakologie MeSH
- molekulární modely * MeSH
- soli chemie MeSH
- techniky syntetické chemie * MeSH
- vazba proteinů MeSH
- Publikační typ
- časopisecké články MeSH
Aqueous extracts of aerial flowering parts of five Agrimonia species (Rosaceae): Agrimonia coreana Nakai, Agrimonia japonica (Miq.) Koidz, Agrimonia procera Wallr., Agrimonia eupatoria L. and Agrimonia leucantha Kunze were investigated on their antioxidant activity, measured using five different methods; the best was the extract from A. procera with IC50 values from 6 to 29 μg/mL. All the extracts displayed inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) at the tested concentration of 100 μg/mL. We found the highest inhibition of cholinesterase in the extract of A. japonica with inhibition 70.4% for AChE and 79.8% for BuChE. These findings are statistically significant in comparison with those of other extracts (p < 0.001). The phytochemical analyses showed that the antioxidant activity of Agrimonia extracts can be affected especially by hexahydroxydiphenoyl (HHDP)-glucose and quercetin glycosides, and inhibition of cholinesterases by apigenin, luteolin and quercetin glycosides.
- MeSH
- acetylcholinesterasa metabolismus MeSH
- Agrimonia chemie klasifikace MeSH
- antioxidancia izolace a purifikace farmakologie MeSH
- apigenin izolace a purifikace farmakologie MeSH
- butyrylcholinesterasa metabolismus MeSH
- cholinesterasové inhibitory izolace a purifikace farmakologie MeSH
- fytonutrienty chemie MeSH
- luteolin izolace a purifikace farmakologie MeSH
- quercetin izolace a purifikace farmakologie MeSH
- rostlinné extrakty chemie farmakologie MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- fytoterapie metody MeSH
- HIV infekce * etiologie imunologie terapie MeSH
- hluchavkovité MeSH
- inhibitory HIV fúze * MeSH
- inhibitory HIV-integrasy * MeSH
- inhibitory HIV-proteasy * MeSH
- klinické zkoušky, fáze II jako téma MeSH
- Lentivirus patogenita růst a vývoj MeSH
- lidé MeSH
- retrovirové infekce MeSH
- rostlinné extrakty MeSH
- Simaroubaceae MeSH
- virion imunologie MeSH
- Check Tag
- lidé MeSH
