RESUMEN
OBJECTIVES: To investigate the protective effect and underlying mechanism of Inula japonica (TEIJ) in the treatment of acute lung injury (ALI). METHODS: Protective effects of TEIJ in the inflammation and oxidative stress were studied in lipopolysaccharide (LPS)-induced ALI mice. Meanwhile, Western blot and real-time qPCR were carried out to investigate the underlying mechanism of TEIJ for ALI as well as immunohistochemistry. KEY FINDINGS: TEIJ significantly alleviated the course of ALI via suppressing the interstitial infiltrated inflammatory cells, the increase of inflammatory factors and the decrease of anti-oxidative factors. TEIJ inactivated the MAPK/NF-κB signalling pathway to suppress the transcription of its downstream target genes, such as TNF-α, IL-6, etc. Meanwhile, TEIJ activated the Keap1/Nrf2 signalling pathway to regulate expression levels of Nrf2 and its target proteins. The results of LC-QTOF-MS/MS indicated potential active constituents of I. japonica, terpenoids and flavonoids. Additionally, terpenoids and flavonoids synergistically alleviated LPS-induced ALI depending on MAPK/NF-κB and Keap1/Nrf2 signalling pathways. CONCLUSION: I. japonica could be considered a potential agent to treat ALI via regulating the MAPK/NF-κB and Keap1/Nrf2 signalling pathways.
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Lesión Pulmonar Aguda , Inula , Animales , Ratones , Lesión Pulmonar Aguda/metabolismo , Flavonoides/farmacología , Inflamación/metabolismo , Inula/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Lipopolisacáridos/farmacología , Pulmón , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Estrés Oxidativo , Espectrometría de Masas en Tándem , Terpenos/farmacologíaRESUMEN
Biseuphoids A (1) and B (2), two unprecedented ent-abietane-type diterpenoid dimers linked by monomeric blocks through C-17-C-12' and C-17-C-11', respectively, were isolated from Euphorbia fischeriana, along with their biogenesis related diterpenoid monomers, 17-hydroxyjolkinolide B (3), caudicifolin (4), and fischeriabietane C (5). Their structures were elucidated by extensive spectroscopy assisted by quantum chemical NMR and ECD calculations. The unusual dimeric skeletons are possibly derived from the adduct of diterpenoid monomers through Michael-like reactions. The novel dimers 1 and 2 exhibited inhibitory activities on soluble epoxide hydrolase (sEH) with IC50 values of 8.17 and 5.61 µM, respectively. Molecular dynamics studies illustrated that both 1 and 2 can occupy the catalytic pocket of sEH by forming stable hydrogen bonds with the key amino acid residues including Gln384, Asn378, Pro361, Ala365, Asn366, and Asn472.
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Diterpenos , Euphorbia , Abietanos/química , Diterpenos/química , Epóxido Hidrolasas/metabolismo , Euphorbia/química , Estructura Molecular , Raíces de Plantas/química , PolímerosRESUMEN
Bislangduoids A and B, a novel class of dimeric diterpenoids based on ent-abietanes tethered by C-17-C-15' bridge, were identified as trace components from a traditional Chinese medicine Euphorbia fischeriana (Langdu). Bislangduoid A features a highly oxidized scaffold incorporating a cage-like pentacyclic core. Their structures were elucidated by extensive spectroscopic techniques, electronic circular dichroism, and NMR calculations. The biosynthetic pathway for the dimeric skeleton and the unique caged moiety via Michael and acetal-formation reactions was proposed. Bislangduoid A showed pronounced cytotoxicity against HepG2 cells through the mitochondria-dependent apoptosis pathway.
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Antineoplásicos , Diterpenos , Euphorbia , Abietanos/química , Abietanos/farmacología , Diterpenos/química , Diterpenos/farmacología , Euphorbia/química , Estructura Molecular , Raíces de Plantas/química , PolímerosRESUMEN
Cumulative evidence indicates that mitochondria dysfunction plays an important role in tumour treatment. Given the limited efficacy and toxicity of current mitochondria-targeted drugs, research into effective mitochondria-targeted anticancer agents remains an irresistible general trend. In this study, it was found that dehydrocrenatidine (DEC), a ß-carbolin alkaloid isolated from Picrasma quassiodes, displays a promising growth inhibitory effect in vitro and in vivo by inducing apoptosis of hepatocellular carcinoma (HCC) cells. Mechanistically, we provided that the possible target of DEC against HCC cells was determined by isobaric labels for relative and absolute quantification assay and validated them using further experiments. The results suggested that DEC can target and regulate the function of mitochondrial complexes I, III and IV, affecting oxidative phosphorylation and ultimately leading to mitochondrial dysfunction to exert its anti-HCC effects. In addition, the combination of DEC and sorafenib showed a synergistic effect and was also associated with mitochondrial dysfunction. Importantly, DEC did not show significant toxicity in mice. This study provided a new insight into underlying mechanisms in DEC-treated HCC cells, suggesting that DEC might be a mitochondrial targeting lead compound.
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Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis , Carbolinas , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Proliferación Celular , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Ratones , MitocondriasRESUMEN
Carbendazim (CBZ), a broad-spectrum pesticide frequently detected in fruits and vegetables, could trigger potential toxic risks to mammals. To facilitate the assessment of health risks, this study aimed to characterize the cytochrome P450 (CYPs)-mediated metabolism profiles of CBZ by a combined experimental and computational study. Our results demonstrated that CYPs-mediated region-selective hydroxylation was a major metabolism pathway for CBZ in liver microsomes from various species including rat, mouse, minipig, dog, rabbit, guinea pig, monkey, cow and human, and the metabolite was biosynthesized and well-characterized as 6-OH-CBZ. CYP1A displayed a predominant role in the region-selective hydroxylation of CBZ that could attenuate its toxicity through converting it into a less toxic metabolite. Meanwhile, five other common pesticides including chlorpyrifos-methyl, prochloraz, chlorfenapyr, chlorpyrifos, and chlorothalonil could significantly inhibit the region-selective hydroxylation of CBZ, and consequently remarkably increased CBZ exposure in vivo. Furthermore, computational study clarified the important contribution of the key amino acid residues Ser122, and Asp313 in CYP1A1, as well as Asp320 in CYP1A2 to the hydroxylation of CBZ through hydrogen bonds. These results would provide some useful information for the metabolic profiles of CBZ by mammalian CYPs, and shed new insights into CYP1A-mediated metabolic detoxification of CBZ and its health risk assessment.
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Sistema Enzimático del Citocromo P-450 , Microsomas Hepáticos , Animales , Bencimidazoles , Carbamatos , Citocromo P-450 CYP1A2/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Hidroxilación , Microsomas Hepáticos/metabolismo , Especificidad de la EspecieRESUMEN
Metabolites from fungi are a major source of natural small molecule drugs in addition to plants, while fungal derived terpenoids have been confirmed to have great potentials in many diseases. Aspergillus fungi are distributed in every corner of the earth, and their terpenoid metabolites exhibit promising diversity in term of both their chemistry and bioactivity. This review attempted to provide timely and comprehensive coverage of chemical, biosynthesis, and biological studies on terpenoids discovered from the genus Aspergillus, including mono-, sesqui-, di-, sester-, tri-, and meroterpenoids, in the last decade. The structural characteristics, biosynthesis, and pharmacological activities of 288 terpenoids were introduced.
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Productos Biológicos , Terpenos , Aspergillus , Productos Biológicos/farmacología , Hongos , PlantasRESUMEN
Intestinal commensal fungi are vital to human health, and their metabolites play a key role in the reciprocal relationship. In the present work, eighteen alkaloids and seven monoterpenoids were isolated from the fermentation of the human intestinal fungus Penicillium oxalicum SL2, including seven undescribed alkaloids (penicilloxalines A-G), three undescribed monoterpenoids (penicilloxalines H-J), and fifteen reported compounds. The structures of the isolated compounds were identified by HRESIMS, 1D and 2D NMR, electronic circular dichroism spectra and quantum chemical calculations. Some metabolites displayed moderate agonistic effects against the pregnane X receptor (PXR), whereas (6R)3,7-dimethyl-6,7-dihydroxy-2(Z)-octenoic acid displayed a significant agonistic effect against the farnesoid X receptor (FXR) with an EC50 value of 0.43 µM, which was verified by investigating FXR downstream target genes and proteins, such as small heterodimer partner 1 (SHP1), fibroblast growth factor (FGF), and bile salt export pump (BSEP).
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Penicillium , Receptor X de Pregnano , Receptores Citoplasmáticos y Nucleares , Humanos , IntestinosRESUMEN
Sargentodoxa cuneata (Oliv.) Rehd. et Wils is a traditional Chinese medicine to treat acute appendicitis, rheumarthritis, abdominal pain, and painful menstruation for a long history. The investigation of S. cuneata led to the isolation and identification of twenty-three secondary metabolites, including two new compounds, sargentodoxosides A (1) and B (2), and twenty-one known ones (3-23). Their structural characterization was conducted by HRESIMS, 1 D and 2 D NMR spectra. All the isolated compounds were assayed for their agonistic activities against the farnesoid X receptor (FXR). Nine of the isolated compounds displayed significant agonistic effects against FXR at 0.1 µM, suggesting that they could be served as potential agents for the development of FXR agonists.
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Medicina Tradicional China , Ranunculales , Ranunculales/químicaRESUMEN
Abstract Gut bacterial β-glucuronidase (GUS) can reactivate xenobiotics that exert enterohepatic circulation- triggered gastrointestinal tract toxicity. GUS inhibitors can alleviate drug-induced enteropathy and improve treatment outcomes. We evaluated the inhibitory effect of Polygonum cuspidatum Siebold & Zucc. and its major constituents against Escherichia coli GUS (EcGUS), and characterized the inhibitory mechanism of each of the components. Trans-resveratrol 4'-O-β-D-glucopyranoside (HZ-1) and (-)-epicatechin gallate (HZ-2) isolated from P. cuspidatum were identified as the key components and potent inhibitors. These two components displayed strong to moderate inhibitory effects on EcGUS, with Ki values of 9.95 and 1.95 μM, respectively. Results from molecular docking indicated that HZ-1 and HZ-2 could interact with the key residues Asp163, Ser360, Ile 363, Glu413, Glu504, and Lys 568 of EcGUS via hydrogen bonding. Our findings demonstrate the inhibitory effect of P. cuspidatum and its two components on EcGUS, which supported the further evaluation and development of P. cuspidatum and its two active components as novel candidates for alleviating drug-induced damage in the mammalian gut.
RESUMEN
ß-Carboline alkaloid harmaline (HA) is a candidate drug molecule that has been proven to have broad and significant biological activity. Herein, the effects of HA on the riboflavin (RF)-sensitized photooxidation under aerobic conditions were studied for the first time. The photooxidation reaction of HA catalyzed by RF is triggered by UV light at 365 nm and shows a time-dependent stepwise reaction process. Seven transformed products, including five undescribed compounds, oxoharmalines A-E (1-4 and 7), and two known compounds, N-(2-(6-Methoxy-2-oxoindolin-3-yl)ethyl)acetamide (5) and harmine (6), were isolated and identified from the reaction system, following as the gradual oxidation mechanisms. The rare polymerization and dehydrogenation processes in radical-mediated photocatalytic reactions were involved in the process. The transformed products 2-7 exhibited significant neuroprotective activity in a model of H2O2-introduced injury in SH-SY5Y cells, which suggested that the products of the interaction between HA and vitamins may be beneficial to health.
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Harmalina/farmacología , Fármacos Neuroprotectores/farmacología , Riboflavina/metabolismo , Carbolinas , Línea Celular Tumoral , Harmina , Humanos , Estructura Molecular , Oxidación-Reducción , Rayos UltravioletaRESUMEN
Two undescribed ent-abietane-type diterpenoid dimers with nonacyclic backbone formed by intermolecular [4 + 2] cycloaddition into a spirocyclic skeleton, bisfischoids A (1) and B (2), along with a known one fischdiabietane A (3), were identified from Euphorbia fischeriana Steud. Their structures were elucidated by extensive spectroscopic analysis, ECD and NMR calculation combined with DP4+ probability analysis, as well as X-ray diffraction. The anti-inflammatory potential of dimers 1-3 were examined using their inhibitory effects on soluble epoxide hydrolase (sEH), which revealed that 1 and 2 exhibited promising activities with inhibition constant (Ki) of 3.20 and 1.95 µM, respectively. Further studies of molecular docking and molecular dynamics indicated that amino acid residue Tyr343 in the catalytic cavity of sEH was the key site for their inhibitory function.
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Antiinflamatorios/farmacología , Medicamentos Herbarios Chinos/farmacología , Epóxido Hidrolasas/antagonistas & inhibidores , Euphorbia/química , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Epóxido Hidrolasas/metabolismo , Humanos , Medicina Tradicional China , Estructura Molecular , Relación Estructura-ActividadRESUMEN
Intestinal commensal fungi are vital to human health, and their secondary metabolites play a key role in the reciprocal relationship. In the present study, the first example of 2,3-seco ergot alkaloids belonging to clavine-type were isolated from the fermentation of human intestinal fungus Aspergillus fumigatus CY018, including two pairs of diastereoisomers, secofumigaclavines A (3) and B (4) and secofumigaclavines C (5) and D (6), one analogue features a highly unsaturated skeleton, secofumigaclavine E (7), along with two known ones, fumigaclavines C (1) and D (2). Their structures were identified based on extensive spectroscopic data in a combination of quantum chemical calculations. Moreover, a single-step operation of semi-synthetic reaction based on riboflavin (RF)-dependent photocatalysis was performed to obtain the novel 2,3-seco ergot alkaloids 3 and 5 from their biosynthetic precursors 1 and 2. All the isolated compounds were evaluated for their anti-inflammatory activity. Among them, secofumigaclavine B (4) could bind to MD2 with a low micromole level of the equilibrium dissociation constant measured by surface plasmon resonance (SPR), and suppress TLR4-mediated NF-κB signaling pathway in RAW264.7 cells, resulting in its anti-inflammatory effect. Molecular dynamics revealed that amino acid residue Tyr131 played a key role in the interaction of secofumigaclavine B (4) with MD2. These findings suggested that secofumigaclavine B (4) could be considered as a potential candidate for the development of MD2 inhibitors.
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Antiinflamatorios/uso terapéutico , Aspergillus fumigatus/efectos de los fármacos , Alcaloides de Claviceps/uso terapéutico , Antiinflamatorios/farmacología , Alcaloides de Claviceps/farmacología , HumanosRESUMEN
Soluble epoxide hydrolase (sEH) is a potential drug target to treat inï¬ammation and neurodegenerative diseases. In this study, we found that the extract of Inula britanica exhibited significantly inhibitory effects against sEH, therefore, we investigated its phytochemical constituents to obtain seven new compounds together with sixteen known ones (1-20), including two pairs of novel enantiomers, (2S,3S)-britanicafanin A (1a), (2R,3R)-britanicafanin A (1b), (2R,3S)-britanicafanin B (2a), and (2S,3R)-britanicafanin B (2b), and three new lignans britanicafanins C-E (3-5). Their structures were determined by HRESIMS, 1D and 2D NMR, and electronic circular dichroism (ECD) spectra as well as quantum chemical computations. All the isolates were evaluated for their inhibitory effects against sEH, compounds 1-3, 5-7, 9, 10, 13, 14, and 17-20 showed significant inhibitory effects against sEH with IC50 values from 3.56 µM to 26.93 µM. The inhibition kinetics results indicated that compounds 9, 10, 13, and 19 were all uncompetitive inhibitors, and their inhibition constants (Ki) values were 7.11, 1.99, 4.06, and 8.78 µM, respectively. Their potential interactions were analyzed by molecular docking and molecular dynamics (MD), which suggested that amino acid residues Asp335 and Asn359, especially Gln384, played an important role in the inhibition of compounds 10 and 13 on sEH, and compounds 10 and 13 could be considered as the potential candidates for the development of sEH inhibitors.
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Productos Biológicos/metabolismo , Productos Biológicos/farmacología , Epóxido Hidrolasas/antagonistas & inhibidores , Epóxido Hidrolasas/metabolismo , Inula/química , Simulación de Dinámica Molecular , Inhibidores Enzimáticos/metabolismo , Inhibidores Enzimáticos/farmacología , Epóxido Hidrolasas/química , Cinética , Simulación del Acoplamiento Molecular , Unión Proteica , Conformación Proteica , SolubilidadRESUMEN
Inhibition of soluble epoxide hydrolase (sEH) is considered to be an effective treatment for inflammation-related diseases, and small molecules origin from natural products show promising activity against sEH. Two undescribed protostanes, 3ß-hydroxy-25-anhydro-alisol F (1) and 3ß-hydroxy-alisol G (2) were isolated from Alisma orientale and identified as new sEH inhibitors with IC50 values of 10.06 and 30.45 µM, respectively. Potential lead compound 1 was determined as an uncompetitive inhibitor against sEH, which had a Ki value of 5.13 µM. In-depth molecular docking and molecular dynamics simulations revealed that amino acid residue Ser374 plays an important role in the inhibition of 1, which also provides an idea for the development of sEH inhibitors based on protostane-type triterpenoids.
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Alisma/química , Inhibidores Enzimáticos/farmacología , Epóxido Hidrolasas/antagonistas & inhibidores , Triterpenos/farmacología , Inhibidores Enzimáticos/química , Epóxido Hidrolasas/química , Concentración 50 Inhibidora , Modelos Moleculares , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Estructura Molecular , Farmacocinética , Extractos Vegetales/química , Extractos Vegetales/farmacología , Conformación Proteica , Triterpenos/químicaRESUMEN
Gut bacterial ß-glucuronidase (GUS) plays a pivotal role in the metabolism and reactivation of a vast of glucuronide conjugates of both endogenous and xenobiotic compounds in the gastrointestinal tract of human, which has been implicated in certain drug-induced gastrointestinal tract (GI) toxicity in clinic. Inhibitors of gut microbial GUS exhibited great potentials in relieving the drug-induced GI toxicity. In this study, Selaginella tamariscina and its major biflavonoid amentoflavone (AMF) were evaluated for their inhibitory activity against Escherichia coli GUS. Two selective probe substrates for GUS (a specific fluorescent probe substrate for GUS, DDAOG and a classical drug substrate for GUS, SN38G) were used in parallel for charactering the inhibition behaviors. Both the extract of S. tamariscina and its major biflavonoid AMF displayed evident inhibitory effects on GUS, and the IC50 values of AMF against GUS mediated DDAOG and SN-38G hydrolysis were 0.62 and 0.49 µM, respectively. Inhibition kinetics studies indicated that AMF showed mixed type inhibition for GUS-mediated DDAOG hydrolysis, while displayed competitive type inhibition against GUS-mediated SN-38G hydrolysis, with the Ki values of 0.24 and 1.25 µM, respectively. Molecular docking studies and molecular dynamics stimulation results clarified the role of amino acid residues Leu361, Ile363, and Glu413 in the inhibition of AMF on GUS. These results provided some foundations for the potential clinical utility of S. tamariscina and its major biflavonoid AMF for treating drug-induced enteropathy.
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Biflavonoides/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Glucuronidasa/antagonistas & inhibidores , Selaginellaceae/química , Aminoácidos/metabolismo , Bacterias/efectos de los fármacos , Bacterias/metabolismo , Escherichia coli/efectos de los fármacos , Escherichia coli/metabolismo , Tracto Gastrointestinal/microbiología , Glucurónidos/metabolismo , Hidrólisis/efectos de los fármacos , Cinética , Simulación del Acoplamiento Molecular/métodos , Simulación de Dinámica MolecularRESUMEN
As a genus of the Asteraceae, Inula is widely distributed all over the world, and several of them are being used in traditional medicines. A number of metabolites were isolated from Inula species, and some of these have shown to possess ranges of pharmacological activities. The genus Inula contains abundant sesquiterpenoids, such as eudesmanes, xanthanes, and sesquiterpenoid dimers and trimers. In addition, other types of terpenoids, flavonoids, and lignins also exist in the genus Inula. Since 2010, more than 300 new secondary metabolites, including several known natural products that were isolated for the first time from the genus Inula. Most of them exhibited potential bioactivities in various diseases. The review aimed to summarize the advance of recent researches (2010-2020) on phytochemical constituents, biosynthesis, and pharmacological properties of the genus Inula for providing a scientific basis and supporting its application and exploitation for new drug development.
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Inula/química , Extractos Vegetales , Desarrollo de Medicamentos , Humanos , Estructura Molecular , Extractos Vegetales/biosíntesis , Extractos Vegetales/química , Extractos Vegetales/farmacologíaRESUMEN
Four new alkaloids (1-4) and one known alkaloid were isolated from the stems of Picrasma quassioides. The structures of these isolated compounds were elucidated by spectroscopic analyses, a combination of computer-assisted structure elucidation software (ACD/Structure Elucidator) and gauge-including atomic orbital (GIAO) calculation of 1 D NMR data. All compounds were evaluated for their cytotoxic activities against hepatocellular carcinoma HepG2 and Hep3B cells. However, they did not show obvious inhibitory activities.[Figure: see text].
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Alcaloides , Neoplasias Hepáticas , Picrasma , Alcaloides/farmacología , Computadores , Humanos , Estructura MolecularRESUMEN
The genus Alisma contains 11 species distributed worldwide, of which at least two species (A. orientale [Sam.] Juzep. and A. plantago-aquatica Linn.) have been used as common herbal medicines. Secondary metabolites obtained from the genus Alisma are considered to be the material basis for the various biological functions and medicinal applications. In this review, we mainly focused on the recent investigations of secondary metabolites from plants of the genus Alisma and their biological activities, with the highlighting on the diversity of the chemical structures, the biosynthesis of interesting secondary metabolites, the biological activities, and the relationships between structures and bioactivities.
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Alisma/química , Fitoquímicos/uso terapéutico , Plantas Medicinales/química , HumanosRESUMEN
Carboxylesterase 2 (CES 2), plays a pivotal role in endobiotic homeostasis and xenobiotic metabolism. Protostanes, the major constituents of the genus Alisma, display a series of pharmacological activities. Despite the extensive studies of pharmacological activities, the investigation on inhibitory effects of protostanes against CES 2 is rarely reported. In this study, the inhibitory activities of a library of protostanes (1-25) against human CES 2 were investigated for the first time, using 6,8-dichloro-9,9-dimethyl-7-oxo-7,9-dihydroacridin-2-yl benzoate (DDAB) as the specific fluorescent probe for human CES 2. Compounds 1, 2, 7, 8, 12, 13, 18, 19, and 25 showed strong inhibitory effects towards CES 2. For the most potent compounds 1, 7, 13, and 25, the inhibition kinetics were further investigated, and these four protostanes were all uncompetitive inhibitors against human CES 2 with the inhibition constant (Ki) values ranging from 0.89 µM to 2.83 µM. In addition, molecular docking and molecular dynamics stimulation were employed to analyze the potential interactions between these protostanes and CES 2, and amino acid residue Gln422 was identified to play a crucial role in the strong inhibition of protostanes towards CES 2.
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Alisma/química , Carboxilesterasa/antagonistas & inhibidores , Extractos Vegetales/química , Extractos Vegetales/farmacología , Triterpenos/química , Triterpenos/farmacología , Acridinas/química , Benzoatos/química , Colorantes Fluorescentes/química , Concentración 50 Inhibidora , Cinética , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Relación Estructura-ActividadRESUMEN
The genus Uncaira (Rubiaceae) comprises of 34 species, many of which are usually used as traditional Chinese medicines (TCMs) to treat hypertension, fever, headache, gastrointestinal illness, and fungal infection. Over the past twenty years, Uncaira species have been paid the considerable attentions in phytochemical and biological aspects, and about 100 new secondary metabolites, including alkaloids, triterpenes, and flavonoids, have been elucidated. This review aims to present a comprehensive and up-to date overview of the biological source, structures and their biosynthetic pathways, as well as the pharmacological of the compounds reported in the genus Uncaria for the past two decades. It would provide an insight into the emerging pharmacological applications of the genus Uncaria.