RESUMO
Seven new bisbibenzyls (1-7) were isolated from the methanol extract of the liverwort Lunularia cruciata along with one previously known bibenzyl and five known bisbibenzyls. The structures of compounds 1-7 were elucidated on the basis of the spectroscopic data. These newly isolated bisbibenzyls may be divided into two groups, the acyclic bisbibenzyls, perrottetins (1-3), and the cyclic analogues, riccardins (4-7). Besides standard perrottetin and riccardin structures (1 and 4, respectively), they contain phenanthrene (3 and 5), dihydrophenanthrene (2), and quinone moieties (6 and 7), rarely found in natural products. The new compounds 3 and 5, as well as the known riccardin G, exhibited cytotoxic activity against the A549 lung cancer cell line with IC50 values of 5.0, 5.0, and 2.5 µM, respectively.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Hepatófitas/química , Células A549 , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , HumanosRESUMO
Hexane extracts of Heracleum verticillatum, H. sibiricum, H. angustisectum, and H. ternatum were studied for their furanocoumarin content antioxidant potential and acetylcholinesterase and α-amylase inhibitory activities. Quantification of the furanocoumarins was performed by 1 H-NMR. Pimpinellin was found to be the main component in the roots of all studied species. Bergapten and imperatorin were the major compounds in the fruits of H. sibiricum and H. verticillatum, respectively, while byakangelicol dominated in H. angustisectum and H. ternatum fruits. The leaf and fruit extracts of H. angustisectum demonstrated the highest DPPH radical scavenging activity and TEAC (IC50 0.58â mg/mL and 1.83â mm, respectively). The root extracts of H. verticillatum and H. angustisectum were found to be the most effective against acetylcholinesterase (IC50 0.30 and 0.34â mg/mL, respectively). The studied extracts were not active or demonstrated a weak inhibitory effect (%Inh. up to 29.7) towards α-amylase.
Assuntos
Antioxidantes/farmacologia , Compostos de Bifenilo/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Furocumarinas/farmacologia , Heracleum/química , Hipoglicemiantes/farmacologia , Picratos/antagonistas & inibidores , Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Animais , Antioxidantes/síntese química , Antioxidantes/química , Diabetes Mellitus Tipo 2/tratamento farmacológico , Electrophorus , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Furocumarinas/síntese química , Furocumarinas/química , Humanos , Hipoglicemiantes/síntese química , Hipoglicemiantes/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Suínos , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/metabolismoRESUMO
The NMR-observable nuclei of the acidic and basic compounds experience pH dependence in chemical shift. This phenomenon can be exploited in NMR titrations to determine p Ka values of compounds, or in pH measurement of solutions using dedicated pH reference compounds. On the other hand, this sensitivity can also cause problems in, for example, metabolomics, where slight changes in pH result in significant difficulties for peak alignment between spectra of set of samples for comparative analysis. In worst case, the pH sensitivity of chemical shifts can prevent unambiguous identification of compounds. Here, we propose an alternative approach for NMR identification of pH-sensitive analytes. The 1H and X (13C, 15N, 31P, ...) chemical shifts in close proximity to the acidic or basic functional group should, when presented as ordered pairs, express piecewise linear correlation with distinct slope, intercept, and range. We have studied the pH dependence of 1H and 31P chemical shifts of the CH3-P moiety in urinary metabolites of nerve agents sarin, soman and VX using 2D 1H-31P fast-HMQC spectroscopy. The 1H and 31P chemical shifts of these chemicals appear in very narrow range, and due to subtle changes in sample pH the identification on either 1H or 31P chemical shift alone is uncertain. However, if the observed 1H and 31P chemical shifts of the CH3-P moiety of individual compounds are presented as ordered pairs, they fall into distinct linear spaces, thus, facilitating identification with high confidence.
Assuntos
Substâncias para a Guerra Química/farmacocinética , Espectroscopia de Ressonância Magnética/métodos , Agentes Neurotóxicos/farmacocinética , Sarina/urina , Soman/urina , Substâncias para a Guerra Química/metabolismo , Humanos , Hidrogênio/metabolismo , Hidrogênio/urina , Concentração de Íons de Hidrogênio , Agentes Neurotóxicos/metabolismo , Isótopos de Fósforo/metabolismo , Isótopos de Fósforo/urina , Sarina/metabolismo , Soman/metabolismoRESUMO
Bisbibenzyls are specialized metabolites found exclusively in liverworts, until recently; they represent chemical markers of liverworts. Their occurrence in vascular plants was noticed in 2007, when they were found in Primula veris subsp. macrocalyx from Russia. This report prompted us to chemically analyze the two most common Serbian Primula species, P. veris subsp. columnae and P. acaulis, in order to determine the presence of bisbibenzyls in them. Our study revealed nine structurally distinct bisbibenzyls (1-9), identified based on 1D and 2D NMR, IR, UV and HRESIMS data. Among them were five previously undescribed compounds (2-6). The remaining compounds found and previously described in the literature were: the bisbibenzyls riccardin C (1), isoperrottetin A (7), isoplagiochin E (8) and 11-O-demethylmarchantin I (9), as well as 4-hydroxyphenylmethylketone (10) and 4-hydroxy-3-methoxyphenylmethylketone (11). Riccardin C was the most dominant bisbibenzyl in both species studied. Previously, it was the first bisbibenzyl found in vascular plants (P. veris subsp. macrocalyx). An assessment of the cytotoxic activity of the isolated compounds against A549 lung cancer and healthy MRC5 cell lines was also the subject of our study. Compounds 6 and 9 exhibited significant cytotoxic activity expressed by IC50 values of 12 µM, but the selectivity was not satisfactory.
Assuntos
Hepatófitas , Primula , Primula/química , Sérvia , Éteres Cíclicos , Hepatófitas/químicaRESUMO
BACKGROUND: Movement of the red flour beetle, Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae), in stored products is mediated by food volatiles and other semiochemicals. RESULTS: In two-way olfactometer assays, T. castaneum was more attracted to wheat bran previously infested with conspecifics than to uninfested bran. Chemical analysis showed that 1-pentadecene was present in the headspace of T. castaneum-infested wheat bran, but not detectable in the headspace of uninfested bran. An olfactometer was used to test the effect on T. castaneum behaviour of 1-pentadecene, and of volatiles from wheat bran with and without 1-pentadecene. The lowest concentration of 1-pentadecene exhibited an attractive effect, compared to the control (n-hexane). Slightly higher concentrations showed a neutral effect, while the highest concentrations repelled T. castaneum. Wheat bran with a low 1-pentadecene concentration was more attractive than wheat bran alone, whereas higher concentrations of 1-pentadecene were repellent. CONCLUSION: The results provide important information on intraspecific, semiochemical-mediated behaviour in T. castaneum, which could potentially be used to develop new methods to monitor the flour beetles in stored products. © 2021 Society of Chemical Industry.
Assuntos
Besouros , Repelentes de Insetos , Tribolium , Animais , Humanos , Repelentes de Insetos/farmacologia , Feromônios/farmacologiaRESUMO
New aurone epoxide, 2,10-oxy-10-methoxysulfuretin (14), and new auronolignan (15), named cotinignan A, were isolated by silica gel column and semipreparative HPLC chromatography from the methylene chloride/methanol extract of Cotinus coggygria Scop. heartwood. In addition, thirteen known secondary metabolites namely sulfuretin, 2,3-trans-fustin, fisetin, butin, butein, taxifolin, eriodictyol, 3',5,5',7-tetrahydroxyflavanone, 3',4',7-trihydroxyflavone, 3-O-methyl-2,3-trans-fustin, 3-O-galloyl-2,3-trans-fustin, ß-resorcylic acid and 3-O-ß-sitosterol glucoside were isolated as well. Their structures were elucidated by 1D and 2D NMR, HR-ESI-MS, IR and UV. Ten out of eleven isolated flavonoids possess 7, 3' and 4' hydroxy groups. These structural features could be considered as chemotaxonomic characteristic of flavonoids from C. coggygria. Cotinignan A (15) represents new subclass of secondary metabolites - auronolignans.
Assuntos
Anacardiaceae/química , Benzofuranos/química , Compostos de Epóxi/química , Madeira/química , Anacardiaceae/metabolismo , Benzofuranos/metabolismo , Chalconas/química , Chalconas/metabolismo , Cromatografia Líquida de Alta Pressão , Compostos de Epóxi/metabolismo , Flavanonas/química , Flavanonas/metabolismo , Flavonoides/análise , Flavonoides/química , Flavonoides/metabolismo , Flavonóis , Hidroxibenzoatos/química , Hidroxibenzoatos/metabolismo , Estrutura Molecular , Extratos Vegetais/química , Metabolismo Secundário , Madeira/metabolismoRESUMO
The synthesis and inhibitory potencies against botulinum neurotoxin serotype A light chain (BoNT/A LC) using in vitro HPLC based enzymatic assay for various steroidal, benzothiophene, thiophene, and adamantane 4-aminoquinoline derivatives are described. In addition, the compounds were evaluated for the activity against BoNT/A holotoxin in mouse embryonic stem cell derived motor neurons. Steroidal derivative 16 showed remarkable protection (up to 89% of uncleaved SNAP-25) even when administered 30 min postintoxication. This appears to be the first example of LC inhibitors antagonizing BoNT intoxication in mouse embryonic stem cell derived motor neurons (mES-MNs) in a postexposure model. Oral administration of 16 was well tolerated in the mouse up to 600 mg/kg, q.d. Although adequate unbound drug levels were not achieved at this dose, the favorable in vitro ADMET results strongly support further work in this series.