Stilbene Derivatives Research Articles

Design and synthesis of 2,6-dihalogenated stilbene derivatives as potential anti-inflammatory and antitumor agents

In present study, three series of 2,6-dihalogenated stilbene derivatives were designed, synthesized, and assayed for anti-inflammatory and cytotoxic activities. All 62 compounds showed potential anti-inflammatory activity in zebrafish model in vivo, and the installation of halogens and pyridines led to significant improved effects. Among them, DHS2u and DHS3u with the substitution of pyridine showed more higher effects than positive drug indomethacin at 20 μM with inhibitory rate of 94.59% and 90.54%, respectively. Besides, DHS3g bearing 2,5-dimethoxy exhibited potent cytotoxic activity against K562 cells with IC50 values 3.12 μM along with a suitable selectivity on normal cell viability. These results showed that 2,6-dihalogenated stilbenes could serve as a bright starting point for the further development as anti-inflammatory and antitumor agents.

Kuwanon X from Mulberry Leaves Exhibits Antiviral Activity Against Human Adenoviruses

Aim: This study aimed to investigate the anti-adenoviral activity of stilbene derivatives from mulberry leaves. Materials & methods: The anti-adenoviral activity was tested against adenoviruses -3 and -7 on human airway epithelial cell models. Cytotoxicity was assessed by LDH assay. Adenoviral DNA was quantified by qPCR. Results: All five tested stilbene derivatives from mulberry leaves exhibited anti-adenoviral activity, with Kuwanon X showing the highest inhibitory effect. Kuwanon X showed no apparent cytotoxicity for a wide range of concentrations. The mechanistic study revealed that Kuwanon X did not affect viral entry and nuclear translocation of the adenoviral genome but reduced viral DNA production. Conclusion: Stilbene derivatives like Kuwanon X from mulberry leaves are good candidates for antiviral treatment against AdV.

Two‐Dimensional Organic Crystals Enabling Anisotropic Photon Transport and Dual‐Color Orthogonally Polarized Laser

AbstractAnisotropic transport of polarized photons in organic 2D crystals provides a great opportunity to construct integrated photonic circuits. However, such study remains a critical challenge limited by the precise orientation of molecular transition dipole moment (TDM) and modification of the interaction between photons and molecular TDM. Herein, a stilbene derivative with strong solid‐state photoluminescence is designed and synthesized. The excellent anisotropic polarization‐dependent waveguide occurs in its parallelogram 2D crystal and further enables 463‐ and 493‐nm lasing emissions along the short and long axes of the crystal, respectively. Polarization measurements show that the two lasers with the different wavelengths have mutually orthogonal linear polarizations. These results provide a new strategy for designing orthogonally polarized lasers in single‐component 2D crystals, which may inspire further development of organic photonic devices with controllable polarization properties.

Homemade Solution of NaOD in D 2 O: Applications in the Field of Stilbene‐ d 1 Synthesis

The development of deuterium-incorporation method is eagerly desired. A solution of sodium deuteroxide in deuterium oxide (NaOD in D2O) was simply prepared by mixing D2O and t-BuONa. Subsequently, the t-BuOD layer, generated under conditions of the salting-out effect, was separate. The purity (volume of the contaminated t-BuOD as side-product) of the homemade NaOD in D2O was evaluated by 1H NMR and Raman analyses. NaOD in D2O was used for the one-pot synthesis of mono-deuterated trans-stilbene (stilbene-d1) in the aqueous Horner-Wadsworth-Emmons reaction. The present method can be widely applied to synthesize the various mono-deuterated stilbene derivatives with high deuterium content. Additionally, the obtained mono-deuterated stilbene derivatives could be successfully converted to various deuterated compounds.

Reversible trans-to-cis photoisomerization and irreversible photocyclization reactions of a Co-coordinated stilbene derivative on chiral di-β-diketonate lanthanide complexes.

Six lanthanide complexes constructed from two chiral β-diketonates (d/l-fbc = 3-heptafluorobutyryl-(+)/(-)-camphorate), the stilbene derivative (E)-N',N'-bis(pyridin-2-ylmethyl)-4-styrylbenzoyl hydrazide (L), a trifluoroacetate anion (CF3CO2 -), and one water molecule, namely [Ln(d/l-fbc)2(L)(CF3CO2)]·H2O (LnC57H54F17N4O8, Ln = La (1, d-fbc), La (2, l-fbc), Sm (3, d-fbc), Eu (4, d-fbc), Eu (5, l-fbc), and Tb (6, d-fbc), were synthesized and characterized by single-crystal X-ray diffraction, 1H-NMR, elemental analysis, IR and UV-vis spectroscopy, and thermal gravimetric analysis. The photoisomerization reactions of these complexes were systematically studied by means of experimental and theoretical calculations. Crystals of complexes 1, 2, 3, and 4 were obtained and belong to the monoclinic crystal system and the C2 chiral space group. The Λ- and Δ-diastereomers coexist in their crystals and no apparent bisignate couplets are observed in their ECD spectra. Among the complexes, the photocyclization reaction is followed by the trans-to-cis photoisomerization reaction and competes with the trans-to-cis photoisomerization, then the photocyclization reaction continues. The photocyclization reaction is irreversible in this stilbene derivative and is delayed in the lanthanide complexes. These results provide a viable strategy for the design of promising new stilbene-attached dual-functional lanthanide-based optical-switching materials.

Recent advances in synthesis of stilbene derivatives via cross-coupling reaction.

The stilbenes are undoubtedly some of the most significant moieties in various bioactive natural and synthetic structures, and they are considered privileged structures. In recent years, the preparation of these structures via cross-coupling reactions has attracted much attention. In the current review, we present a summary of the recent developments in the construction of stilbene and stilbene derivatives by carbon-carbon coupling reactions of organic compounds in the presence of transition metal catalysts or under metal-free conditions. In this context, we outline the features of the important reactions, some product yields, and challenging reaction mechanisms.

Electrochemical deoxygenative homo-couplings of aromatic aldehydes.

An electrochemical deoxygenative homo-coupling of aromatic aldehydes is achieved to selectively access bibenzyl and stilbene derivatives. The protocol allows the homo-coupling of aldehydes to occur after single-electron-reduction at the cathode. Taking advantage of the oxophilicity of triphenylphosphine, the electrochemical deoxygenation proceeds smoothly to give reductive homo-coupling products.

Self-assembly of benzophenone-diphenylalanine conjugate into a nanostructured photocatalyst.

The conjugation of photoactive benzophenone with diphenylalanine yielded a self-assembling photocatalyst that was probed in the E → Z photoisomerisation of stilbene derivatives.

Elicitation of Stilbenes and Benzofuran Derivatives in Hairy Root Cultures of White Mulberry (Morus alba).

Stilbene and benzofuran derivatives isolated from the root of white mulberry (Morus alba) have shown various biological activities, including anti-inflammatory, antioxidant, and antimicrobial properties. The objectives of this study were to develop hairy root cultures and assess the effect of multiple elicitors combinations including (I) methyl-β-cyclodextrin (CD), MgCl2, methyl jasmonate (MeJA), and H2O2, (II) CD, MgCl2, and MeJA and (III) CD, MgCl2, and H2O2, on the production of these bioactive compounds. The highest yields of stilbenes and benzofurans were obtained upon co-treatment with 18 g/L CD, 3 mM H2O2 and 1 mM MgCl2. The stilbenes oxyresveratrol, resveratrol, and 3'-prenylresveratrol accumulated up to 6.27, 0.61, and 5.00 mg/g DW root, respectively. Meanwhile, the aryl benzofurans moracin M and moracin C accumulated up to 7.82 and 1.82 mg/g DW root, respectively. These stilbenes and benzofurans accumulated in the culture medium of the elicited hairy root cultures. They were not detected in the root tissue. However, the oxyresveratrol diglucoside mulberroside A was only detected in the root tissue with yields up to 10.01 mg/g DW. The results demonstrated that co-treatment of white mulberry hairy root cultures with multiple elicitors can significantly enhance production and secretion of stilbenes and benzofurans in this controlled and sustainable axenic culture system.

Cascade Synthesis of Phenanthrenes under Photoirradiation

We report a photoinduced phenanthrene synthesis from aryl iodides and styrenes through an arylation/cyclization cascade. Compared to prior methods, this approach obviates the need for hazardous reagents and provides access to unsymmetrical phenanthrenes with good functional group tolerance. Mechanistic studies revealed that photoexcitation of aryl iodides leads to homolytic C-I bond cleavage. Arylation of styrenes with the formed aryl radical species furnishes stilbene derivatives, which undergo photoinduced cyclization promoted by iodine generated in situ to yield phenanthrene products.

Synthesis and Biological Evaluation of Dipeptide-Based Stilbene Derivatives Bearing a Biheterocyclic Moiety as Potential Fungicides.

The escalating demand for crop production, environmental protection, and food safety warrants the development of new fungicides with greater efficiency, environmental friendliness, and innocuous metabolites to fight against destructive phytopathogens. Herein, we report on the synthesis and antifungal activity of dipeptide-based stilbene derivatives bearing a thiophene-substituted 1,3,4-oxadiazole fragment for the first time. In vitro bioassay indicated that the target compounds had remarkable antifungal potency superior to previously reported counterparts without a dipeptidyl group, of which compound 3c exhibited the highest activity against Botrytis cinerea with EC50 values of 106.1 μg/mL. Moreover, the in vivo protective effect of compound 3c (59.1%) against tomato gray mold was more potent than that of carboxin (42.0%). Preliminary investigations on the mode of action showed that compound 3c induced marked hyphal malformations and increased the membrane permeability of B. cinerea as well as inhibiting mycelial respiration. These promising results suggest that this novel type of molecular framework has great potential to be further developed as alternative fungicides.

AIEE active stilbene based fluorescent sensor with red-shifted emission for vapor phase detection of nitrobenzene and moisture sensing

A unique π-electron rich stilbene-based sensor with significantly enhanced red-shifted fluorescence emission has been synthesized via a Mizoroki-Heck cross-coupling reaction. The strong fluorescence properties of stilbene derivative as a potential fluorescent sensor have been investigated for sensitive and selective detection of hazardous and threatening nitrobenzene (NB) in both solution and vapor phase. The fluorescence emission intensity of stilbene sensor 1 at 474 nm was quenched upon interaction with NB. The fluorescence quenching was attributed to the combined effect of dominant smaller and adjustable size of NB and photo-induced electron transfer (PET) process. Stilbene sensor 1 is the first active bathochromic shifted fluorescent sensor with AIEE property was developed for both solution and vapor phase detection of NB. Possible interactions of stilbene sensor 1 with NB was evaluated by UV–vis., fluorescence, density functional theory (DFT) calculations, and 1H NMR titration experiment. Additionally, non-covalent interaction (NCI), Frontier molecular orbitals (FMOs) and interaction energy were studied by using Gaussian 09 software. Moreover, test strips were fabricated to accomplish contact mode detection of NB. Further, stilbene sensor 1 was successfully applied for trace detection of NB in real water samples.

HPLC-HRESI-MSn Characterization of Polyphenolic Compounds in the Stem Bark of Chlorophora regia A. Chev (Moraceae)

Isolation and identification of secondary metabolites from medicinal plants could be tedious and time consuming. Therefore, any technique that could be used to confirm the identity of medicinal plant constituents without isolating them will save time and resources. Chlorophora similar to many genera in the Moraceae family have been demonstrated to be rich sources of polyphenolic compounds with important biological activities. The current study was designed to employ HRESI-MSn analyses to qualitatively examine isolated polyphenolic compounds from the stem bark of Chlorophora regia. Based on the HRESI-MSn data obtained, the fragmentation patterns of the compounds under study will be proposed and could be used in their identification in a matrix. Five polyphenolic compounds were successfully isolated and purified using various chromatographic techniques including column chromatography, thin-layer chromatography (TLC) and preparative HPLC. The structures of the isolated compounds were elucidated by in-depth analyses of their 1D and 2D NMR and mass spectroscopic data. HRESI-MS/MS was further used to characterize the isolated compounds. Five polyphenolic compounds including three Diels-Alder type adducts: sanggenon C, kuwanol E and chalcomoracin; two stilbene derivatives: chlorophorin and isochlorophorin were isolated from the stem bark. The tandem MS fragmentation patterns of the compounds in positive mode, were successfully proposed. The fragments obtained and proposed fragmentation patterns of the isolated compounds could be employed qualitatively in the identification of the studied polyphenolic compounds in a matrix.

Azobenzene derivatives with activity against drug-resistant Candida albicans and Candida auris.

Increasing resistance against antimycotic drugs challenges anti-infective therapies today and contributes to the mortality of infections by drug-resistant Candida species and strains. Therefore, novel antifungal agents are needed. A promising approach in developing new drugs is using naturally occurring molecules as lead structures. In this work, 4,4'-dihydroxyazobenzene, a compound structurally related to antifungal stilbene derivatives and present in Agaricus xanthodermus (yellow stainer), served as a starting point for the synthesis of five azobenzene derivatives. These compounds prevented the growth of both fluconazole-susceptible and fluconazole-resistant Candida albicans and Candida auris strains. Further in vivo studies are required to confirm the potential therapeutic value of these compounds.

Methoxy and methylthio-substituted trans-stilbene derivatives as CYP1B1 inhibitors – QSAR study with detailed interpretation of molecular descriptors

A quantitative structure–activity relationship (QSAR) model was built using multiple linear regression (MLR) to predict the ability of series methyl and/or methylthio trans -stilbene derivatives to inhibit CYP1B1. Twenty-four compounds with their activity expressed as the negative log of the IC 50 value (pIC50 [M]) were split into a training (20 compounds) and a test set (four compounds) using Kennard and Stone algorithm. Molecular descriptors were calculated using alvaDesc software after compound optimization in the Gaussian 09 package in PL-Grid. The model characterized by the best validation parameters (R 2 TRAIN = 0.954, Q 2 LOO = 0.898, R 2 TEST = 0.880) was chosen based on the chemometric method – cluster analysis. The applicability domain has been determined, indicating that the regression model can give reliable prediction. The study shows that the inhibitory activity against CYP1B1 of the methyl and/or methylthio trans -stilbene derivatives can be predicted by RDF035m, Mor10m, Eig04_AEA(bo), RDF070s, MaxDD descriptors. Finally, the paper attempts to interpret three-dimensional descriptors by assessing the impact of interatomic interactions, following the partition of molecules into fragments, on the final value of descriptors.

Cyano-substituted stilbene (CSS)-based conjugated polymers: Photophysical properties exploration and applications in photodynamic therapy

Conjugated polymers (CPs) have attracted great attention due to their excellent optical properties (such as large absorption cross section, signal amplification, high photostability etc.). As representative electron acceptors and organic small molecules which are easy to be synthesized and modified, cyano-substituted stilbene (CSS) derivatives are widely used to construct photoelectrical materials. Despite donor-acceptor (D-A) conjugated polymers based on CSS have been applied in sensing and super-resolution imaging, systematic studies about the effects of different CSS structures on the photophysical properties of CPs have rarely been reported. Therefore, we have synthesized a series of D-A conjugated polymer nanoparticles (CP NPs) based on different CSS units, and found that the photophysical properties of CP NPs including the bandgap and ΔES-T were closely associated with the structure of CSS derivatives. Moreover, the introduction of tetraphenylethylene (TPE) can relieve the aggregation-caused quenching (ACQ) effects of CSS conjugated polymers to varying degrees. The theoretical calculation further corroborated that by regulating the number and distribution of cyanide groups in the repeating units, the stronger D-A strength resulted in a redshift in the emission spectrum and the more efficient capacity of total ROS (1O2, O2•− and •OH) generation. We then selected CP6-TAT NPs, with the near infrared (NIR) emission and best ФPS, to characterize its performance in photodynamic therapy (PDT). It was revealed that CP6-TAT NPs can be regarded as an ideal candidate for PDT. The results provided a new reference for regulating the structure-effect relationship of CPs and a comprehensive method for constructing photosensitizers based on CPs.

Six undescribed derivatives of stilbene isolated from Lindera reflexa Hemsl. and their anti-tumor and anti-inflammatory activities

Six undescribed stilbene derivatives Reflexanbene DH (1–4, 6) and Reflexanbene J (5), as well as one known stilbene 3,5-dimethoxystilbene (7), were isolated from the dried roots of Lindera reflexa Hemsl. Their structures and absolute configurations were elucidated using spectroscopy and electronic circular dichroism (ECD) analysis. In cytotoxic assays, moderately inhibitory activities of Reflexanbene F (3) against MGC80–3 and A549 cell lines were observed, with IC50 values of 15.42 and 5.09 μM, respectively. The IC50 value of Reflexanbene E (2) on A549 cell lines was 19.78 μM. The isolated compounds were also tested for their inhibitory effect against LPS-induced NO and IL-6 production in RAW 264.7 cells. In particular, Reflexanbene J (5) and Reflexanbene H (6) showed significant inhibition of NO production in LPS-stimulated macrophage RAW 264.7 cells at the concentration of 20 μM. Furthermore, the expression of IL-6 protein in the LPS-induced RAW 264.7 cells can also be significantly inhibited by different concentrations (5, 10 and 20 μM, p < 0.05 or p < 0.01) of compounds 1–7.

Isorhapontigenin prevents β‑amyloid‑associated cognitive impairments through activation of the PI3K/AKT/GSK‑3β pathway.

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disease that is the most common cause of dementia in the elderly. Aβ1‑42 is significantly associated with memory deficits and it can increase the level of acetylcholine, promote the activity of acetylcholinesterase (AChE), and cause cognitive dysfunction. Isorhapontigenin (ISO) is a stilbene derivative that has antioxidant, anti‑tumor, and anti‑inflammatory effects. However, it is still unclear whether ISO can affect β‑amyloid‑associated cognitive impairments. In this study, we found that ISO improved cognitive dysfunction induced by Aβ1‑42 in rats. It inhibited the Aβ‑induced activation of M1 microglia and reduced the release of inflammatory cytokines. It alleviated amyloid beta‑induced oxidative stress and led to an overall improvement in AD symptoms. Cellularly, we found that ISO alleviated Aβ‑induced inflammation and oxidative stress by activating the PI3K/AKT/GSK‑3β pathway and ultimately improved cognitive dysfunction in AD rats.

Induction of the Prenylated Stilbenoids Arachidin-1 and Arachidin-3 and Their Semi-Preparative Separation and Purification from Hairy Root Cultures of Peanut (Arachis hypogaea L.).

Prenylated stilbenoids such as arachidin-1 and arachidin-3 are stilbene derivatives that exhibit multiple pharmacological activities. We report an elicitation strategy using different combinations of cyclodextrin, hydrogen peroxide, methyl jasmonate and magnesium chloride to increase arachidin-1 and arachidin-3 production in peanut hairy root cultures. The treatment of hairy root cultures with cyclodextrin with hydrogen peroxide selectively enhanced arachidin-1 yield (132.6 ± 20.4 mg/L), which was 1.8-fold higher than arachidin-3. Similarly, cyclodextrin combined with methyl jasmonate selectively enhanced arachidin-3 yield (178.2 ± 6.8 mg/L), which was 5.5-fold higher than arachidin-1. Re-elicitation of the hairy root cultures further increased the levels of arachidin-1 and arachidin-3 by 24% and 42%, respectively. The ethyl acetate extract of the culture medium was consecutively fractionated by normal- and reversed-phase column chromatography, followed by semi-preparative HPLC purification on a C18 column to yield arachidin-1 with a recovery rate of 32% and arachidin-3 with a recovery rate of 39%, both at higher than 95% purity. This study provided a sustainable strategy to produce high-purity arachidin-1 and arachidin-3 using hairy root cultures of peanuts combined with column chromatography and semi-preparative HPLC.

Structures and Anti-Inflammatory Evaluation of Phenylpropanoid Derivatives from the Aerial Parts of Dioscorea polystachya.

Seven undescribed phenylpropanoid constituents, including three new bibenzyl derivatives (1–3) along with four new benzofuran stilbene derivatives (4–7), were isolated from the aerial parts of Dioscorea polystachya. The structures of these compounds were elucidated using a combination of spectroscopic analyses, including UV, IR, HRESIMS, 1D, and 2D NMR. Further, all the compounds were evaluated on the anti-inflammatory activity for their inhibition of nitric oxide (NO) production by RAW 264.7 macrophages cells, and some of them (1–3 and 6) displayed inhibitory activity with IC50 values in the range of 9.3–32.3 μM. Moreover, compound 3 decreased the expression of iNOS in Western blot analysis, suggesting compound 3 is mediated via the suppression of an LPS-induced NF-κB inflammasome pathway.