Furan Moiety Research Articles

Silver(I) pyridinyl complexes with benzothiazole, thiophene, and furan moieties: DNA/protein-binding, antibacterial, antioxidant, and anticancer studies.

We have synthesized and characterized nine Ag(I) complexes of Schiff bases containing thiophene, furan, and pyridine moieties for in vitro antibacterial, antioxidant, anticancer activities, and DNA/bovine serum albumin(BSA) binding studies. Based on the analytical and spectral analyses, a linear geometry was proposed for all the Ag(I) complexes, except for one (with the furan moiety), which formed a distorted T-shaped geometry. UV-vis absorption studies on the interactions of calf thymus-DNA (CT-DNA) with the nine Ag(I) complexes pointed to an intercalative binding mode. With a binding constant Kb of 3.75 × 105 M-1 , the complex bearing a benzothiazole moiety (1) interacted stronger with CT-DNA than the rest of the complexes. Fluorescence spectroscopic data revealed that the complexes had a modest binding affinity for BSA through static quenching. The complexes displayed good antioxidant properties, especially those with a benzothiazole moiety. Notable antibacterial activities against methicillin-resistant Staphylococcus aureus, Staphylococcus aureus, Salmonella typhimurium, Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae were observed for complexes with the furan and thiophene moieties. The in vitro anticancer studies of selected complexes against three cancer cell lines showed that the complexes were more effective against the inhibition of the growth of cervical cancer cells relative to cisplatin.

Boron Trifluoride Etherate-Controlled Reactions of Methyl Enol Ethers: Selective Synthesis of Dihydrofuro[3,2-c]chromenone and Furo[3,2-c]chromenone Derivatives

AbstractA facile one-step synthetic approach to dihydrofuro-[3,2-c]chromenones and furo[3,2-c]chromenones by the reaction of methyl enol ethers with 4-hydroxycoumarins under metal-free conditions is presented. Dihydrofuro[3,2-c]chromenones and furo[3,2-c]-chromenones were selectively obtained by controlling the stoichiometry of boron trifluoride diethyl etherate. An unexpected aryl-group migration followed by aromatization of the furan moiety, leading to a variety of furo[3,2-c]chromenone derivatives in good yields, is reported.

Serrulatane diterpenoids with unusual side chain modifications from root bark of Eremophila longifolia

The plant genus Eremophila is endemic to Australia and widespread in arid regions. Root bark extract of Eremophila longifolia (R.Br.) F.Muell. (Scrophulariaceae) was investigated by LC-PDA-HRMS, and dereplication suggested the presence of a series of diterpenoids. Using a combination of preparative- and analytical-scale HPLC separation as well as extensive 1D and 2D NMR analysis, the structures of 12 hitherto unreported serrulatane diterpenoids, eremolongine A-L, were established. These structures included serrulatanes with unusual side chain modifications to form hitherto unseen skeletons with, e.g., cyclopentane, oxepane, and bicyclic hexahydro-1H-cyclopenta[c]furan moieties. Serrulatane diterpenoids in Eremophila have recently been shown to originate from a common biosynthetic precursor with conserved stereochemical configuration, and this was used for tentative assignment of the relative and absolute configuration of the isolated compounds. Triple high-resolution α-glucosidase/α-amylase/PTP1B inhibition profiling demonstrated that several of the eremolongines had weak inhibitory activity towards targets important for management of type 2 diabetes.

Synthesis, in vitro, and in silico studies of novel poly‐heterocyclic compounds bearing pyridine and furan moieties as potential anticancer agents

Thirteen novel poly‐heterocyclic compounds containing pyridine and furan moieties were synthesized and fully characterized by 1H NMR, 13C NMR, FTIR, and elemental analysis. The optimized geometry of the most stable conformation of the synthesized compounds was determined at the DFT/B3LYP level of theory. Frontier molecular orbitals, molecular electrostatic potential, and atoms in molecules analysis were performed to better understand the electronic properties, reactivity, and intermolecular interactions. The cytotoxicity of all compounds was assessed In vitro against MCF-7 and A-2780 cell lines using the MTT assay. Among them, compounds 2c, 3c, 3d, 4a, and 4c at 0.1 µM concentration showed more potent cytotoxicity against the MCF-7 cells than the reference drug docetaxel. On the other hand, compounds 2c, 3a, 3c, and 4c are more cytotoxic against the A-2780 cell line compared to the standard at the same concentration. The docking studies revealed an excellent affinity for the active site of the human topoisomerase-IIβ enzyme, which may explain the promising cytotoxicity of these classes of molecules. The in silico evaluation of ADMET parameters indicated good pharmacokinetic properties of all the investigated compounds.

Fast Initiating Furan-Containing Hoveyda-Type Complexes: Synthesis and Applications in Metathesis Reactions

Two new ruthenium complexes with chelating-ether benzylidene ligands bearing a furan moiety were synthesized and characterized, including X-ray crystallography. They initiated fast, also at 0 °C, and were found to be highly active in a variety of ring-closing, ene-yne, and cross-metathesis reactions, including an active pharmaceutical ingredient (API) model, which makes them good candidates for the transformation of complex polyfunctional compounds that require mild reaction conditions.

Effect of thiophene, furan moieties and zinc ions on melamine-based porous polyaminals properties and catalytic activity on CO2 cycloaddition reaction

A new series of melamine-based porous polyaminals containing thiophene or furan moieties of different size in the polymer network were prepared and fully characterized. The new polyaminals were N-rich polymers with nitrogen content between 10 and 28%, exhibited micro-, meso- or macroporosity, depending on the type and size of the thiophene or furan moiety with specific surface areas in the range of 23–490 m2/g. The CO2 uptakes were moderated, between 1 and 5% and those polyaminals with higher CO2 uptake capacity were selected as catalysts to promote the conversion of CO2 into cyclic carbonate and also to prepare the corresponding zinc complexes, which were used as catalysts in the same reaction. The selected catalysts showed good catalytic performance working under much milder reaction conditions (CO2 pressure of 4 bar, 80 °C, 0.1 mol % of cocatalyst) than the examples of melamine-based polyaminals published so far for this reaction.

Water-reducible and self-healing acrylic coatings based on Diels-Alder reversible reaction

A novel aqueous coating based on Diels-Alder (DA) chemistry is presented. In such material, three peculiar features, namely optical transparency, self-healing ability and water-reducibility, are integrated. The thermal-reversibility of the polymer network is achieved by crosslinking a random terpolymer of furfuryl methacrylate (FMA), methacrylic acid (MAA) and 2-ethyl-hexyl methacrylate (EHMA) with an aliphatic bismaleimide through a DA reaction between furan and maleimide moieties. The effectiveness of the thermal reversibility is proved by differential scanning calorimetry, solubility tests and multiple scratch-repair cycles. The adoption of an aliphatic bismaleimide as crosslinker imparts a great transparency and absence of color to the thermally responsive coating as assessed by UV–vis spectroscopy. Thanks to the presence of the carboxyl moiety in the MAA units, dispersion in water after neutralization is enabled, ensuring the production of a water-reducible coating systems with added functionalities.

Ruthenium(II)-catalyzed C(3)–H arylation of furan moiety in fuberidazole derivatives

An efficient selective C(3)–H arylation of furan ring in 2-(furan-2-yl)benzimidazoles, derivatives of fuberidazole fungicide, with aryl bromides catalyzed by [RuCl2(cymene)]2/ pivalic acid system has been accomplished. High selectivity of the process may be accounted for by the action of benzimidazol-2-yl substituent as the directing group.

Development of a mechanism-based biomarker for Dioscorea bulbifera L. exposure and hepatotoxicity in rats

BackgroundDioscorea bulbifera L. (DBL) is a common herbal medicine where furanoterpenoid diosbulbin B (DSB) is a major component responsible for its hepatotoxicity. The metabolic oxidation of the furan moiety of DSB, resulting in covalent binding to hepatic protein, is considered to initiate its liver injury. PurposeWe aimed to develop a mechanism-based plasma protein adduction-based biomarker to determine DBL exposure and to predict the onset of hepatotoxicity induced by DBL. MethodsRats were intragastrically treated with DBL extract, and the plasma samples were collected. Plasma ALT and AST were measured with commercial kits. Plasma protein modification was determined by immunoblot assay. Assessment of DSB-induced protein adduction was achieved by LC-MS/MS analysis of complete proteolytic digestion of adducted protein to pyrroline derivative A4 using pronase enzyme. The structure of the resulting pyrroline derivatives was confirmed by NMR. ResultsPlasma protein of rats treated with DBL extract was covalently modified by the metabolite of DSB. Pyrroline derivative A4 was detected in proteolytic digestion of plasma obtained from rats administered DBL extract. The protein adduction elevated with the increase in the dosage of DBL extract. A detectable level of plasma was observed 10 days after withdrawal of DBL extract post 30-day continuous administration. In addition, the elevation trend of plasma ALT was found to be proportional to the accumulation trend of pyrroline derivative A4. ConclusionDSB-derived plasma protein adduction correlated well with the exposure of DBL in rats. The protein adduction may be used as a good biomarker for diagnosis of DBL-induced liver injury and a useful indicator for DBL medication plans.

Sarglafuran A, a lindenane-type sesquiterpene dimers with unique furan ring from the leaves of Sarcandra glabra

Sarglafuran A (1), a new [4 + 2] type lindenane sesquiterpene dimer with an unique furan ring moiety, and a pair of new [2 + 2] type dimeric lindenane epimers, sarglalactones N and O (2 and 3), were isolated from the leaves of Sarcandra glabra. Their structures were elucidated by comprehensive spectroscopic analyses, and the absolute configurations of these compounds were determined by single crystal X-ray diffraction or CD exciton chirality method. In addition, a possible biosynthetic pathway of the unique furan ring moiety in 1 had been proposed. Their cytotoxicity against MCF-7 and MDA-MB-231, together with the inhibitory activity against nitric oxide (NO) production of LPS-induced RAW264.7 macrophages were evaluated.

Synthesis, Characterization and Antifungal Activity of Novel Thiazolo-Pyrimidine Fused Heterocycles

In medicinal chemistry, nitrogen and sulphur containing heterocyclic compounds are well known for their therapeutic properties.(1) Among them thiazole and pyrimidine derivatives possess diverse pharmaceutical activities.(2,3) More particularly thiazolo-pyrimidine fused shows various therapeutically activities like, anticancer, antimicrobial, antibacterial effects, antiviral ,etc (4-7). Such type of fused heterocycles containing furan and naphthalene moieties has not been developed. Thus, the aim of the present work to study the novel fused thiazolo-pyrimidine derivatives, their characterization and antifungal activity. (scheme-1).

Anticancer, antioxidant, antiviral and antimicrobial activities of Kei Apple (Dovyalis caffra) fruit

Secondary plant metabolites remain one of the key sources of therapeutic agents despite the development of new approaches for the discovery of medicinal drugs. In the current study, chemical analysis, and biological activities of Kei apple (Dovyalis caffra) methanolic extract were evaluated. Chemical analysis was performed using HPLC and GC–MS. Antiviral and anticancer effect were assessed using the crystal violet technique and activity against human liver cells (HepG2), respectively. Antibacterial activity was tested with the disc diffusion method. The obtained results showed that chlorogenic acid (2107.96 ± 0.07 µg/g), catechin (168 ± 0.58 µg/g), and gallic acid (15.66 ± 0.02 µg/g) were the main bioactive compounds identified by HPLC techniques. While, compounds containing furan moieties, as well as levoglucosenone, isochiapin B, dotriacontane, 7-nonynoic acid and tert-hexadecanethiol, with different biological activities were identified by GC–MS. Additionally, inhibition of 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) scavenging was 79.25% at 2000 µg/mL, indicating its antioxidant activity with IC50 of 728.20 ± 1.04 µg/mL. The tested extract exhibited potential anticancer activity (58.90% toxicity) against HepG2 cells at 1000 µg/mL. Potential bacterial inhibition was observed mainly against Escherichia coli and Proteus vulgaris, followed by Staphylococcus aureus and Bacillus subtilis with a diameter of growth inhibition ranging from 13 to 24 mm. While weak activities were recorded for fungi Candida albicans (10 mm). The extract showed mild antiviral activity against human coronavirus 229E with a selective index (SI) of 10.4, but not against human H3N2 (SI of 0.67). The molecular docking study's energy ratings were in good promise with the experiment documents of antibacterial and antiviral activities. The findings suggest that D. caffra juice extract is a potential candidate for further experiments to assess its use as potential alternative therapeutic agent.

Equipping Coiled-Coil Peptide Dimers With Furan Warheads Reveals Novel Cross-Link Partners.

Using a coiled-coil peptide dimer as a model system to explore furan reactivity, we describe novel cross-link partners of furan warheads for site-specific cross-linking. We demonstrate that replacement of weak interhelical ionic contacts with a furan moiety and its potential cross-link partner affords covalently connected coiled-coil motifs upon furan activation. We describe for the first time the reaction of the activated furan warhead with cysteine and tyrosine, besides the previously reported lysine, thus enhancing the versatility of the furan cross-link methodology by the possibility to target different amino acids. The present in vitro validation of “furan-armed” α-helices provides further grounds for exploiting furan technology in the development of furan-modified ligands/proteins to target proteins in a covalent way through various amino acid side chains.

Novel fluorinated pyrazolo[1,5-a]pyrimidines: In a way from synthesis and docking studies to biological evaluation

Starting compound 2-cyanomethyl-7-(thiophen-2-yl)-5-trifluoromethylpyrazolo[1,5-a]pyrimidine-3-carbonitrile 3 reacts with aromatic aldehydes, aromatic diazonium salts, o-hydroxybenzaldehyde and isatin, a series of new fluorinated pyrazolo[1,5-a]pyrimidine derivatives were obtained. Additionally, the enamine derivative of compound 3 reacts with each of hydrazine hydrate and guanidine hydrochloride to form fluorinated ployheterocycles. The newly synthesized compounds were characterized by spectral data (IR, 1H NMR, 13C NMR and MS) and elemental analyses. Some selected compounds were tested in vitro for antiviral activity against Coxsackie virus B4(COX-B4), Rift Valley Fever (RVF), Vesicular stomatitis virus (VSV), and Encephalomyocarditis (EMCV) virus. The results of the antiviral evaluation of some new compounds 3, 5c, 5i, 7b, and 15 showed good antiviral activity against the tested viruses, for example compound 5c containing the withdrawing group (Cl) showed 26.6% inhibition against COX-B4, while 5i containing the furan moiety showed decreased activity compared to 5c (21%). Furthermore, compound 15 which is a fused compound showed an inhibitory effect 23%. Also, compounds 3, 5c, 5i, 7b and 15 were evaluated against the HCV-NS3 protease using Sovaldi as a control. The results showed that compound 5c had a good inhibitory effect on hepatitis C virus protease (HCV-NS3), with an IC50 of 7.33 ± 0.51 μg/ml, compared to IC50 of Sovaldi 3.20 ± 1.33 μg/ml. The virucidal activity of 5c was also determined by direct and indirect methods. The direct method showed moderate antiviral activity (0.76 log(10) / ml, corresponding to the percentage depletion of the virus infectivity titer of 13.8%. In contrast, the indirect method showed better antiviral activity, which was dependent on the time of application (1.75 log (10) /ml), which is 31.828%. Molecular Operating Environment software (MOE, 2015.10) was used to dock compounds 3, 5c, 15 compared to Sovaldi as a reference drug with the active site of co-crystallized B-Raf (PDB code: 3II5). The results showed good formation of hydrogen bonds between the functional groups NH, CO, CN, S atom and N atom of the target compounds with His 573, Thr 528, Cys 531, Glu 500, lle 591, Asp 593 and Gly 595 residues in terms of bond length and binding energy compared to Sovaldi. In addition, Absorption Metabolism Distribution Excretion studies (ADME) are used in the drug development process to study various factors that influence drug action and efficacy. Thus ADME was performed for compounds 3, 5c and 15 and showed that compound 3 could be absorbed through the gastrointestinal tract compared to other compounds tested.

Impact of Furan Substitution on the Optoelectronic Properties of Biphenylyl/Thiophene Derivatives for Light-Emitting Transistors.

Biphenylyl/thiophene systems are known for their ambipolar behavior and good optical emissivity. However, often these systems alone are not enough to fabricate the commercial-grade light-emitting devices. In particular, our recent experimental and theoretical analyses on the three-ring-constituting thiophenes end capped with biphenylyl have shown good electrical properties but lack of good optical properties. From a materials science perspective, one way to improve the properties is to modify their structure and integrate it with additional moieties. In recent years, furan moieties have proven to be a potential substitution for thiophene to improve the organic semiconductive materials properties. In the present work, we systematically substituted different proportions of furan rings in the biphenylyl/thiophene core and studied their optoelectronic properties, aiming toward organic light-emitting transistor applications. We have found that the molecular planarity plays a vital role on the optoelectronic properties of the system. The lower electronegativity of the O atom offers better optical properties in the furan-substituted systems. Further, the furan substitution significantly affects the molecular planarity, which in turn affects the system mobility. As a result, we observed drastic changes in the optoelectronic properties of two furan-substituted systems. Interestingly, addition of furan has reduced the electron mobility by one fold compared to the pristine thiophene-based derivative. Such a variation is interpreted to be due to the low average electronic coupling in furan systems. Overall, systems with all furan and one ring of furan in the center end capped with thiophene have shown better optoelectronic properties. This molecular architecture favors more planarity in the system with good electrical properties and transition dipole moments, which would both play a vital role in the construction of an organic light-emitting transistor.

Synthesis and anticancer activity of new carbohydrazide derivatives bearing furan moiety

Synthesis and anticancer activity of new carbohydrazide derivatives bearing furan moiety

Reversible, controllable white-light emission of dye systems by dynamic covalent furan moiety exchange.

New exo-Diels-Alder adduct dyes were synthesized. Pure exo and endo dye isomers were isolated and prepared. Two high-quality, blue-light emitting crystals were obtained. X-ray single crystal diffraction reveals the precise structure of the exo isomer, and longer Diels-Alder bonds (1.59 Å) than common C-C bonds (1.54 Å). The adduct dye displays high intramolecular energy transfer efficiency from the pyrene donor to the dansyl acceptor, where blue-violet donor emission is prohibited. By dynamic furan moiety exchange, the donor fluorescence restores, which combines with complementary green-yellow acceptor fluorescence to give white-light emission of the dye systems. White and green-light emitting dye systems could be reversibly, controllably, and mutually transformed.

A NIR Emitting Cyanine with Large Stokes' Shift for Mitochondria and Identification of their Membrane Potential Disruption.

An NIR emitting (λem ≈730 nm) cyanine probe ExCy was synthesized in good yields by extending the π-conjugation length (i. e., with furan moiety) to the donor-accepter system. ExCy exhibited a large Stokes' shift (Δλ≈100 nm) due to strong intramolecular charge transfer (ICT), and high fluorescence quantum yield (Φfl ≈0.47 in DCM). Due to its low fluorescence in an aqueous environment (Φfl ≈0.007 in H2 O), the probe exhibited the potential of achieving a large fluorescence turn-on upon entering a hydrophobic cellular environment. Fluorescence confocal microscopy studies revealed that ExCy was readily excitable with a far-red laser line (i. e., 640 nm) while the corresponding emission was collected in the NIR region. ExCy exhibited excellent selectivity towards live cell mitochondria according to the co-localization studies. The probe also exhibited high photostability, long-term imaging ability and wash-free staining ability, when being applied to live cells. Our studies indicated that the mitochondrial localization of ExCy was dependent on the membrane potential of the mitochondria. ExCy was successfully utilized as a mitochondrial membrane potential dysfunction indicator to visually identify cells with mitochondrial dysfunction via fluorescence confocal microscopy. ExCy was further examined for potential in vivo imaging of zebrafish.

An efficient electron transport properties of fullerene functionalized with tricyanovinyldihydrofuran (TCF)

The charge mobility is an important property of organic optoelectronic materials. Fullerene (C60) derivatives have been extensively used as electron acceptor materials in optoelectronics. However, the effect of structural modification of fullerene with furan moieties on its charge transport characteristics has rarely been studies. Herein, we synthesized (E)-2-(3-cyano-5,5-dimethyl-4-styrylfuran-2(5H)-ylidene)malononitrile (S1), phenyl functionalized C60 (S2) and furan functionalized C60 (S3) using S2 as a reactant. These compounds have been fully characterized by means of FTIR, 1H NMR, 13C NMR spectroscopy and MALDI-TOF spectrometry for their structure. The photophysical and electrochemical characteristics of S1, S2 and S3 were studied to understand the effect of structural architecture change of C60over redox and optical properties. The electron mobility inS1, S2 and S3 was studied using space-charge limiting current (SCLC) model where, S3 shows 18x higher mobility than the most used acceptor PB61BM. After thermal treatment at 70 °C, S1, S2 and S3 displayed a maximum electron mobility (μe) of (1.39 ± 0.30) × 10−3, (1.3 ± 0.24) × 10−4 and (1.84 ± 0.26) × 10−3 cm2/V.s respectively. Further, computational method was employed to model the S1, S2 and S3electronic structure and frontier electron transitions. Both HOMO and LUMO states drop by exactly the same amount upon structural change from S2 to S3 to give equal Eg when calculated using B3LYP. This suggests that conjoint molecular architecture of TCF and fullerene exhibits interesting photophysical and electrochemical an efficient charge transport properties.

Direct Conversion of Hydrazones to Amines using Transaminases

Transaminase enzymes (TAms) have been widely used for the amination of aldehydes and ketones, often resulting in optically pure products. In this work, transaminases were directly reacted with hydrazones in a novel approach to form amine products. Several substrates were investigated, including those with furan and phenyl moieties. It was determined that the amine yields increased when an additional electrophile was added to the reaction mixture, suggesting that they can sequester the hydrazine released in the reaction. Pyridoxal 5’‐phosphate (PLP), a cofactor for transaminases, and polyethylene glycol (PEG)‐aldehydes were both found to increase the yield of amine formed. Notably, the amination of (S)‐(−)‐1‐amino‐2‐(methoxymethyl)pyrrolidine (SAMP) hydrazones gave promising results as a method to form chiral β‐substituted amines in good yield.