RESUMEN
Pepper (Piper nigrum L.) is a widely used spice plant known for its fruits and roots, which serve as flavor enhancers in culinary applications and hold significant economic value. Despite the popularity of pepper fruits, their roots remain relatively understudied, with limited research conducted on their bioactive components. This study focused on discovering and separating the primary bioactive amide alkaloids found in pepper roots. The process involved using the antioxidant activity of crude fractions and the Global Natural Products Social Molecular Networking analysis platform. The process led to the discovery of 23 previously unknown hydroxyl-amide alkaloids. Notably, compounds 11, 12, and 14 showed excellent antioxidant activity, while compound 11 exhibited significant inhibitory effects on mushroom tyrosinase. Theoretical exploration of enzyme-ligand interactions was conducted through molecular docking and molecular dynamics simulation. The findings of this study highlight the potential of hydroxyl-amide alkaloids as antioxidant products and natural food preservatives in the pharmaceutical and food cosmetic industries.
RESUMEN
Six previously undescribed 2, 9-deoxyflavonoids (1/2a, 1/2b, 6, and 7), along with six known compounds (3-5, and 8-10), were isolated from the twigs and leaves of Aglaia odorata. Their structures were determined by a combination of spectral analysis, ECD calculation and enzymatic hydrolysis assay. Surprisingly, (±) aglaindanone E (11a, 11b) were unexpectedly formed as the derivatives of compounds 3-6 when exposed to ambient natural light. Furthermore, the plausible biosynthetic pathway of 2, 9-deoxyflavonoids was proposed and chemically mimicked. In biological activity assay, compounds 1/2a, 1/2b, 4, and 6 showed potential protective effects in the 0.75%CSE-induced BEAS-2B cells injury model.
RESUMEN
Axially chiral compounds are well known in medicinal chemistry of natural products, but their absolute configurations and bioactivities are rarely reported and studied. In this study, eleven undescribed axially chiral dihydrophenanthrene dimers, as well as twenty-five known dihydrophenanthrenes, were isolated from the entire plant of Pholidota yunnanensis. Their structures were elucidated by comprehensive spectroscopic analysis. A method for determining the absolute configurations of enantiomers was developed based on the rotational barriers and calculated ECD spectra. Additionally, the activities of all isolated compounds were assessed in LPS-induced BV-2 microglial cells. Most dihydrophenanthrenes exhibited significant NO inhibitory activities, and compound 7 showed the most potent inhibitory effect with an IC50 value of 1.5 µM, compared to the positive control minocycline. The immunofluorescence and western blot results revealed that compound 7 suppressed the expression of Iba-1, iNOS and COX-2 in LPS-stimulated BV-2 microglial cells.
Asunto(s)
Lipopolisacáridos , Microglía , Fenantrenos , Fenantrenos/farmacología , Fenantrenos/química , Fenantrenos/aislamiento & purificación , Animales , Ratones , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Estructura Molecular , Microglía/efectos de los fármacos , Microglía/metabolismo , Relación Estructura-Actividad , Dimerización , Relación Dosis-Respuesta a Droga , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Óxido Nítrico/metabolismo , Orchidaceae/química , Línea Celular , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/aislamiento & purificación , EstereoisomerismoRESUMEN
A phytochemical study of the ethanol extract from Ailanthus altissima (Mill.) Swingle leaves resulted in the isolation of four new monoterpenoids (1-3, 5). The structures were elucidated using HRESIMS data, NMR spectroscopic data, quantum chemical calculations for NMR and ECD, and custom DP4+ probability analysis. Additionally, the absolute configuration of sugar was determined by acid hydrolysis. Compounds 1-4 are cyclogeraniane monocyclic monoterpenes, while compound 5 contains an acyclic mycrane monoterpenes skeleton. Anti-tyrosinase, anti-acetylcholinesterase, and anti-butyrylcholinesterase activities were tested. Compound 1 showed notable anti-acetylcholinesterase activity, and compound 3 exhibited significant inhibitory effects on anti-tyrosinase activity. Furthermore, the potential binding sites of compounds 1 and 3 were predicted by molecular docking.
Asunto(s)
Ailanthus , Simulación del Acoplamiento Molecular , Monoterpenos , Fitoquímicos , Hojas de la Planta , Ailanthus/química , Estructura Molecular , Monoterpenos/aislamiento & purificación , Monoterpenos/farmacología , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Hojas de la Planta/química , Inhibidores de la Colinesterasa/aislamiento & purificación , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/química , Monofenol Monooxigenasa/antagonistas & inhibidores , Acetilcolinesterasa/metabolismo , Butirilcolinesterasa/metabolismoRESUMEN
Fifty compounds including seven undescribed (1, 13, 18-20, 30, 31) and forty-three known (2-12, 14-17, 21-29, 32-50) ones were isolated from the extract of the twigs and leaves of Aglaia odorata with anti-neuroinflammatory activities. Their structures were determined by a combination of spectral analysis and calculated spectra (ECD and NMR). Among them, compounds 13-25 were found to possess tertiary amide bonds, with compounds 16, 17, and 19-21 existing detectable cis/trans mixtures in 1H NMR spectrum measured in CDCl3. Specifically, the analysis of the cis-trans isomerization equilibrium of tertiary amides in compounds 19-24 was conducted using NMR spectroscopy and quantum chemical calculations. Bioactivity evaluation showed that the cyclopenta[b]benzofuran derivatives (2-6, 8, 10, 12) could inhibit nitric oxide production at the nanomolar concentration (IC50 values ranging from 2 to 100 nM) in lipopolysaccharide-induced BV-2 cells, which were 413-20670 times greater than that of the positive drug (minocycline, IC50 = 41.34 µM). The cyclopenta[bc]benzopyran derivatives (13-16), diterpenoids (30-35), lignan (40), and flavonoids (45, 47, 49, 50) also demonstrated significant inhibitory activities with IC50 values ranging from 1.74 to 38.44 µM. Furthermore, the in vivo anti-neuroinflammatory effect of rocaglaol (12) was evaluated via immunofluorescence, qRT-PCR, and western blot assays in the LPS-treated mice model. The results showed that rocaglaol (12) attenuated the activation of microglia and decreased the mRNA expression of iNOS, TNF-α, IL-1ß, and IL-6 in the cortex and hippocampus of mice. The mechanistic study suggested that rocaglaol might inhibit the activation of the NF-κB signaling pathway to relieve the neuroinflammatory response.
Asunto(s)
Aglaia , Lipopolisacáridos , Óxido Nítrico , Animales , Ratones , Aglaia/química , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Óxido Nítrico/metabolismo , Estructura Molecular , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Masculino , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/aislamiento & purificación , Benzofuranos/farmacología , Benzofuranos/química , Benzofuranos/aislamiento & purificación , Línea Celular , Hojas de la Planta/químicaRESUMEN
Seven undescribed neovibsane-type diterpenoids (1-7) were isolated from the leaves of Viburnum odoratissimum. Their planar structures and relative configurations were elucidated based on a combination of 1D and 2D NMR analysis. The absolute configurations were confirmed by Rh2(OCOCF3)4-induced ECD analysis and comparison of experimental and TDDFT-calculated ECD spectrum. Based on the empirical results of the ECD of in situ formed Rh-complexes, rapid determination of the absolute configuration of C-14 within vibsane-type diterpenoids was proposed. In addition, 3 exhibited a high neuroblastoma cell protective effect of 81.8 % at 50 µM (the control group showed a neuroblastoma cell protective effect of 56.2 % at 50 µM).
Asunto(s)
Diterpenos , Neuroblastoma , Viburnum , Viburnum/química , Estructura Molecular , Diterpenos/química , Hojas de la Planta/químicaRESUMEN
From the 95% ethanol aqueous extract of the roots of Clausena lansium, six previously undescribed alkaloids (1, 2a, 2b, 15, 24a, 24b), a pair of prenylated phenylpropenols (26a, 26b), two coumarins (27, 28), and two undescribed sesquiterpenes (37, 38) were isolated and identified using spectroscopic and electron circular dichroism data, together with thirty-two known compounds. The absolute configurations of three alkaloids (3a, 3b, 4a) were determined for the first time. In vitro assay showed that alkaloids 7, 10, 12, 19, and furanocoumarins 34, 35 displayed inhibitory effects on the production of nitric oxide in lipopolysaccharide (LPS)-induced BV-2 microglial cells, which were stronger than that of the minocycline (positive control). RT-PCR results indicated that indizoline (7) could inhibit the expression of pro-inflammatory factors (IL-1ß, TNF-α, and IL-6) in LPS-treated BV-2 cells.
Asunto(s)
Alcaloides , Clausena , Estructura Molecular , Clausena/química , Microglía , Lipopolisacáridos/farmacología , Carbazoles/química , Alcaloides/química , Óxido NítricoRESUMEN
Four pairs of neolignan enantiomers (±)-1- (±)-4 with a distinctive isochroman moiety, including seven undescribed compounds, were isolated and identified from the fruits of Crataegus pinnatifida. Structural characterization of these compounds was established through comprehensive spectroscopic analyses, as well as quantum chemical calculations of ECD and NMR data. The preliminary bioassay displayed that compounds (+)-2 and (±)-3 exerted protective activities against H2O2-induced human neuroblastoma SH-SY5Y cells compared with the positive control. These bioactive compounds could be potential candidates for further pharmaceutical applications.
Asunto(s)
Crataegus , Lignanos , Neuroblastoma , Humanos , Lignanos/farmacología , Frutas/química , Crataegus/química , Peróxido de Hidrógeno/farmacologíaRESUMEN
Three undescribed compounds elephantopuscabers A-C, along with one previously reported compound spirowallichiione, were isolated from Elephantopus scaber L. Their structures were determined via extensive NMR spectroscopic analysis, quantum chemical calculations, and single-crystal X-ray diffraction crystallography. A plausible biosynthetic pathway for spirowallichiione was proposed. All the isolated compounds were tested for their acetylcholinesterase inhibitory activities. Among them, elephantopuscaber B and C displayed promising inhibitory activities against AChE, and the binding sites were predicted by molecular docking.
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Terpenos , Triterpenos , Terpenos/farmacología , Acetilcolinesterasa , Simulación del Acoplamiento Molecular , Estructura MolecularRESUMEN
Four pairs of aryldihydronaphthalene-type lignanamide enantiomers were isolated from Solanum lyratum (Solanaceae). The enantiomeric separation was accomplished by chiral-phase HPLC, and five undescribed compounds were elucidated. Analysis by various spectroscopy and ECD calculations, the structures of undescribed compounds were illuminated. The neuroprotective effects of all compounds were evaluated using H2 O2 -induced human neuroblastoma SH-SY5Y cells and AchE inhibition activity. Among them, compound 4 a exhibited remarkable neuroprotective effects at high concentrations of 25 and 50â µmol/L comparable to Trolox. Compound 1 a showed the highest AchE inhibition with the IC50 value of 3.06±2.40â µmol/L. Molecular docking of the three active compounds was performed and the linkage between the compounds and the active site of AchE was elucidated.
Asunto(s)
Neuroblastoma , Fármacos Neuroprotectores , Solanum , Humanos , Solanum/química , Fármacos Neuroprotectores/química , Simulación del Acoplamiento Molecular , Estereoisomerismo , Estructura MolecularRESUMEN
The regioselectivity for gold(I)-catalyzed intramolecular cycloisomerizations of tryptamine-ynamides has long been elusive despite various synthetic examples of similar substrates being available. Computational studies were carried out to provide insight into the mechanisms and the origin of the substrate-dependent regioselectivity of these transformations. Based on the analyses of non-covalent interactions, distortion/interaction, and energy decomposition on the interactions between the terminal substituent of alkynes and the gold(I) catalytic ligand, the electrostatic effect was determined to be the key factor for α-position selectivity while the dispersion effect was determined to be the key factor for ß-position selectivity. Our computational results were consistent with the experimental observations. This study provides useful guidance for understanding other similar gold(I)-catalyzed asymmetric alkyne cyclization reactions.
RESUMEN
In this study, we designed and synthesized a new class of aggregation-induced emission luminogens, which was inspired and developed from the structure of tetraphenyl-1,3-butadienes derivative (TPB-1) through the minus strategy by removing one of the phenyl groups. Among them, L1 and L4 exhibited an aggregation-induced emission effect and multistimuli-responsive chromic behavior. Moreover, two types of single crystals of L1 were obtained, and their different emission behaviors were elucidated clearly by analyzing the single-crystal data.
RESUMEN
Development of new mechanochromic luminescent (MCL) materials from aggregation-induced emission luminogens (AIEgens) has attracted wide attention due to their potential application in multiple areas. However, rational design and crafting of new MCL materials from the simple AIEgens skeleton is still a big challenge because of the undesirable concentration quenching effect. In this study, we have constructed a new class of MCL materials by adding one phenyl as a new rotator and incorporating one pair of electron donor (D) and acceptor (A) into the system of rofecoxib skeleton. This strategy endowed the compounds (Y1-Y8) with tunable emission behavior and some of them with the AIE effect and reversible MCL behavior. These properties may be caused by the highly twisted conformation and loosely molecular packing modes, which were elucidated clearly by analyzing the data of single-crystal X-ray diffraction, powder X-ray diffraction, and differential scanning calorimetry. Further investigation revealed that Y7 displayed acidochromic property due to the protonation of the nitrogen atom. Moreover, Y7, as a typical compound, showed its potential applications in the area of anticounterfeiting, pH sensor, and LD-specific bioimaging.
Asunto(s)
Colorantes Fluorescentes , Luminiscencia , Colorantes Fluorescentes/química , Lactonas , SulfonasRESUMEN
The development of aggregation-induced emission luminogens (AIEgens) has attracted increasing attention due to their potential applications in various areas in recent years. In this study, a facile conversion from aggregation-caused quenching (ACQ) to aggregation-induced emission (AIE) was achieved by an efficient regioisomerization strategy based on the rofecoxib scaffold. Two compounds, named PYR2 and PYR4, were identified as regioisomers of rofecoxib derivatives to show dramatically different fluorescent properties. Compound PYR2 with an ortho-substituted piperidine group showed typical AIE activity while compound PYR4 with a para-piperidine group exhibited typical ACQ behavior. Notably, compound PYR2 showed polymorphism with two forms of crystals. It was also endowed with reversible mechanochromic luminescence and acidochromic properties. The different fluorescent properties were elucidated by UV/Vis absorption spectroscopy, powder X-ray diffraction, differential scanning calorimetry, and thermogravimetric analyses. Its application as a security ink and in lipid droplets imaging have been demonstrated.
Asunto(s)
Colorantes Fluorescentes , Sulfonas , Colorantes Fluorescentes/química , Lactonas , LuminiscenciaRESUMEN
Glioma, especially the most aggressive type glioblastoma multiforme, is a malignant cancer of the central nervous system with a poor prognosis. Traditional treatments are mainly surgery combined with radiotherapy and chemotherapy, which is still far from satisfactory. Therefore, it is of great clinical significance to find new therapeutic agents. Serving as an inhibitor of differentiation, protein ID2 (inhibitor of DNA binding 2) plays an important role in neurogenesis, neovascularization and malignant development of gliomas. It has been shown that ID2 affects the malignant progression of gliomas through different mechanisms. In this study, a pharmacophore-based virtual screening was carried out and 16 hit compounds were purchased for pharmacological evaluations on their ID2 inhibitory activities. Based on the cytotoxicity of these small-molecule compounds, two compounds were shown to effectively inhibit the viability of glioma cells in the micromolar range. Among them, AK-778-XXMU was chosen for further study due to its better solubility in water. A SPR (Surface Plasma Resonance) assay proved the high affinity between AK-778-XXMU and ID2 protein with the KD value as 129 nM. The plausible binding mode of ID2 was studied by molecular docking and it was found to match AGX51 very well in the same binding site. Subsequently, the cancer-suppressing potency of the compound was characterized both in vitro and in vivo. The data demonstrated that compound AK-778-XXMU is a potent ID2 antagonist which has the potential to be developed as a therapeutic agent against glioma.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Descubrimiento de Drogas , Glioma/tratamiento farmacológico , Proteína 2 Inhibidora de la Diferenciación/antagonistas & inhibidores , Bibliotecas de Moléculas Pequeñas/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Ensayos de Selección de Medicamentos Antitumorales , Glioma/metabolismo , Glioma/patología , Humanos , Proteína 2 Inhibidora de la Diferenciación/metabolismo , Modelos Moleculares , Estructura Molecular , Bibliotecas de Moléculas Pequeñas/síntesis química , Bibliotecas de Moléculas Pequeñas/química , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
Aggregation-induced emission (AIE) has attracted much attention in the past 2 decades. To develop novel AIE-active materials, ACQ-to-AIE transformation via regioisomerization is one of the most straightforward method. However, most of the reported ACQ-to-AIE transformations are achieved by migrating bulky units. In this work, a facile conversion was realized by migrating a small pyrrolidinyl group from para- to ortho-position on the rofecoxib scaffold. As a result, a pair of new isomers named MOX2 and MOX4 exhibited AIE behavior and ACQ activity, respectively. Moreover, MOX2 also showed solvatochromic, mechanochromic, and acidochromic properties with reversible multi-stimulus behavior. Single crystal X-ray analysis of MOX2 revealed that the molecular conformation and its packing mode were responsible for the AIE emission behavior. Further investigation indicated that MOX2 showed high lipid droplets staining selectivity. Taken together, the current work not only provides a new design philosophy for achieving ACQ-to-AIE conversion by migrating a small pyrrolidinyl group but also presents a promising candidate MOX2 for potential applications such as in security ink, optical recording and biological applications.
RESUMEN
In this work, we synthesized a pair of positional isomers by attaching a small electron-donating pyrrolidinyl group at ortho- and para-positions of a conjugated core. These isomers exhibited totally different fluorescent properties. PDB2 exhibited obvious aggregation-induced emission properties. In contrast, PDB4 showed the traditional aggregation-caused quenching effect. Their different fluorescent properties were investigated by absorption spectroscopy, fluorescence spectroscopy, density functional theory calculations and single-crystal structural analysis. These results indicated that the substituent position of the pyrrolidinyl groups affects the twisted degree of the isomers, which further induces different molecular packing modes, thus resulting in different fluorescent properties of these two isomers. This molecular design concept provided a new accurate strategy for designing new aggregation-induced emission luminogens.