Methoxy Derivatives Research Articles

Robust Nonspiro‐Based Hole Conductors for High‐Efficiency Perovskite Solar Cells

AbstractDespite considerable development in performance, both poor operational stability and high costs associated with hole conductors such as 2,2′,7,7′‐tetrakis[N,N‐di(4‐methoxyphenyl)amino]‐9,9′‐spirobifluorene (spiro‐OMeTAD) and Poly[bis(4‐phenyl)(2,4,6‐trimethylphenyl)amine (PTAA) of perovskite solar cells (PSCs) need to be addressed by the research community. Here, two nonspiro hole transporting materials (HTMs), namely HTM‐1 and HTM‐2, are designed and straightforwardly synthesized exhibiting remarkable electrochemical properties and hole mobilities. In particular, the PSC based on the methoxy derivative (HTM‐2) exhibits a remarkable efficiency of 21.2% (stabilized efficiency of 20.8%), which is superior to the benchmark HTM spiro‐OMeTAD (stabilized efficiency of 20.4%). These results establish that the molecular design is effective in improving the performance of PSCs. Importantly, these two HTMs show admissible long‐term stability under different harsh conditions such as thermal stress up to 85 °C, high humidity level of 60% ± 10%, and continuous illumination over 1000 h. These insights allow correlating the impact of molecular design on optoelectronic properties of nonspiro‐based hole conductors with the overall device performance.

Spectroscopic Characterization and Antioxidant Properties of Mandelic Acid and Its Derivatives in a Theoretical and Experimental Approach.

The following article discusses the antioxidant properties of mandelic acid and its hydroxy and methoxy derivatives. The antioxidant capacity of these compounds is determined by DPPH, FRAP, CUPRAC and ABTS. The mechanisms underlying the antioxidant properties are described by BDE, IP, PDE, ETE and PA calculation method values and referenced to experimental data. Thermochemistry, HOMO/LUMO energies, dipole moments, charge distribution, IR, RAMAN, NMR frequencies, binding lengths and angles were calculated using the B3LYP method and the 6-311++G(d,p) basis set. The structure of mandelic acid and its derivatives was determined experimentally using IR and RAMAN spectroscopy.

Obtaining substituted phenol derivatives with potential antimicrobial activity

Objectives. With the growing resistance of pathogenic microorganisms to antibiotics, the development of new antimicrobial drugs offering specific mechanisms of action becomes an urgent task. Only few antimicrobials offer a broad spectrum of activity against gram-positive and gram-negative bacteria, molds, and yeasts. In this regard, the purpose of the work was to develop methods for synthesizing biologically active derivatives of alkyl-substituted phenols (reactions at the hydroxy group) to study their biological effect.Methods. The synthesis of imidazole acetates of substituted phenols was carried out in two stages. At the first stage, the chloroacetyl derivative of the selected compounds was obtained, to which imidazole was then added. O-acylation reactions at the first stage of the synthesis were carried out under varying conditions. The first version of the synthesis was carried out using chloroacetyl chloride as an acylating agent together with a high-boiling solvent. In the second variant, chloroacetic anhydride was used, along with an attempt to replace the solvent with a low-boiling one. A thymol methoxy derivative was additionally synthesized by a known method using methyl iodide and varying the reaction parameters.Results. The parameters of chloroacetylation and methoxylation of aromatic alcohols were optimized with rational selection of solvents and the ratio of reagents in the reactions. Synthesized thymol (2-isopropyl-5-methylphenol) and propofol (2,6-isopropylphenol) derivatives contained imidazole as an additional pharmacophore with affinity for microorganism cell membrane proteins. A thymol methoxy derivative comprising an aromatic ether exhibiting increased hydrophobicity was also obtained. The synthesized compounds were characterized by NMR spectroscopy.Conclusions. Chloroacetyl derivatives of aromatic alcohols can be effectively synthesized by cooling the reaction mixture using an excess quantity of an acylating agent and increasing the reaction time (compared to literature data). The yield of thymol chloroacetate was 75%, while that of propofol chloroacetate was 30%. This can be explained by the sterically hindered reaction of the propofol alcohol group, which has isopropyl substituents at the second and sixth positions of the benzene ring.

Mesogenic Behavior of New Derivatives Containing Azo‐Ester‐Imine Links with Different Substituted Alkoxy Groups as Terminal Tails

AbstractTwo series of ten ester derivatives with four aromatic rings linked together by three different linkages (azo/ester/imine), 4‐((4‐substituted)diazenyl)phenyl 4‐((4‐alkoxybenzylidene)amino)benzoate (IVn X=OCH3 and Vn X=Br) were synthesized. These derivatives have an alkoxy chain in the para position of the phenyl ring with different lengths (n=3, 4, 6, 7, and 12) on one terminal side while the other side was substituted by methoxy and bromo groups linked to the p‐position of phenyl. The structures of all synthesized derivatives were proven by nuclear magnetic resonance (1H‐NMR, 13C‐NMR), elemental analysis (C,H,N), and Fourier‐transform infrared spectroscopy (FT‐IR). The Mesophase textures of the final esters were observed by polarized optical microscopy (POM) and differential scanning calorimetry (DSC). Only the nematic texture was observed in the methoxy derivatives while nematic and smectic A textures were shown in the bromo mesogens. All the homologous showed mesogenic behavior with wide thermal stability. From the results, it was found that the liquid crystalline behaviors of these derivatives are dependent on the substituted group (‐X) and the length of the alkoxy chain. The mesogenic behavior of these compounds was compared with other mesogens that have similar structures.

Synthesis, molecular modeling and antioxidant screening of new thioether-bridged thiadiazole and thiadiazolopyrimidine analogues

The N-aryl-2-((5-(2-cyanoacetamido)-1,3,4-thiadiazol-2-yl)thio)acetamide derivatives 3a-c were prepared and successfully reacted with N,N-dimethylformamide dimethyl acetal (DMF-DMA). The resulting N-thiadiazolyl-2-cyano-3-(dimethylamino)acrylamide derivatives 4a-c were cyclized in boiling acetic acid to yield the corresponding thiadiazolopyrimidine compounds 5a-c. The structural properties of synthesized compounds were studied using DFT/B3LYP level. The HOMO-LUMO energies were employed in determination of some chemical reactivity descriptors. Despite the close energy gap values (ΔEH-L) of the investigated compounds, the data showed that chloro derivatives has the highest energy gap while the methoxy derivatives were the lowest. The synthesized compounds were investigated to explore their antioxidant activities. The results showed that the N-thiadiazolyl-2-cyano-3-(dimethylamino)acrylamides 4a-c had higher inhibition IC50 values (24.27–31.64 µg/mL) than the thiadiazolyl cyanoacetamides 3a-c (34.26–39.33 µg/mL). However, thiadiazolopyrimidines 5a-c presented moderate inhibition with (IC50 = 40.21–44.19 µg/mL) in comparison to ascorbic acid and BHT (Butylated hydroxytoluene) as reference drugs with IC50 = 22.66 and 27.24 µg/mL, respectively. Furthermore, the synthesized compounds were evaluated against (PDB Code-3ML5) using the MOE operation v10.2015.10 database. The inspected synthesized thiadiazole derivatives 3, 4 and 5 revealed H-bond linkages over the receptor through the disparate polar amino acids (Thr 200, Thr 199, Gln 67, His 94, and Lys 91) of larger pocket size of 3ML5. The results of the docking study presented a remarkable agreement with the practical results of the antioxidant activity.

Plant Growth Suppressive Activity of (R)-3-(7'-Aryl-9'-hydroxyprop-8'-yl)coumarin, Structural Isomer of Z-2-Hydroxybenzylidene-γ-butyrolactone-type Lignan.

3-(7'-Aryl-9'-hydroxyprop-8'-yl)coumarin, which is a structural isomer of a Z-2-hydroxybenzylidene-γ-butyrolactone-type lignan, was stereoselectively synthesized and subjected to plant growth regulation examination. (R)-4'-Methoxyphenyl derivative 3 showed stereospecific plant growth suppressive activity. The significance of the presence of hydroxy group at the 9'-position for the activity was clarified. The effect of the substituent at the 7'-aryl group was also shown. The 3'-methoxy, 4'-methoxy, and 4'-trifluoromethyl derivatives 10, 3, and 22 led to the most significant growth suppression of Italian ryegrass roots. The 2'-methoxy derivative 9 and 4'-methoxy derivative 3 provided the most growth suppressive activity against lettuce shoots and roots, respectively.

Docking Investigation on Bis (Nitro Indazolyl) Methanes; Synthesis and Antimicrobial Activity Towards Breast Cancer Applications

: Bismuth (III) nitrate pentahydrate (BN) was found to be a mild and efficient catalyst for the electrophilic condensation of 5-nitroindazole with a wide range of aldehydes to obtain Bis (5-nitro indazolyl) methanes 3 (a-h) at ambient temperature. This was structurally confirmed from FTIR, NMR, and HR-MS technique. Molecular docking studies of all compounds was carried out using breast cancer-causing human estrogen receptor (ER) from Molegro Virtual Docker software. Hydroxy Bis (nitro indazolyl) methanes (3b) were shown better binding affinities and the score obtained was -150.146 Kcal/mol compared with Tamoxifen drug. The major H-bond interactions were observed with the compound 3f and the value was -5.679. The antimicrobial activity results revealed that compounds 3b and 3d showed promising activity against bacteria Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus, and Pseudomonas aeruginosa and maximum inhibition against Aspergillus niger and Aspergillus flavus. Methoxy derivatives of Bis (nitro indazolyl methanes) (3e) have shown better antioxidant activity and low MIC (6.25 µg/ml) observed for the compounds 3a and 3b. The synthesized compounds have a very promising starting point for the development and improvement of anti-breast cancer drugs.

Secondary metabolites from two varieties of Ageratina espinosarum and their chemophenetic significance

Chemical analysis of the hydroalcoholic extracts from the aerial parts of the two accepted varieties of Ageratina espinosarum (A.Gray) R.M. King & H. Rob. (Asteraceae) resulted in the identification of ent-dihydrotucumanol (4), ent-dihydrotucumanoic acid (5), apigenin (19), acacetin (21), apigenin 7,4′-dimethyl ether (22), kaempferol (25), kaempferol 7,4′-dimethyl ether (26), and a mixture of 26 and kaempferol 3,7,4′-trimethyl ether (27) from A. espinosarum var. subintegrifolia; and taxifolin (7), naringenin (9), crysoeriol 4′-methyl ether (10), alysifolinone (11), sakuranetin (12), a mixture of sakuranetin 4′-methyl ether (13) and persicogenin (14), homoeriodictyol (15), and apigenin (19) from A. espinosarum var. espinosarum. Compounds 9, 12, 19 and 25 have been previously isolated of the aerial parts from this plant. Compound 19 was present in both varieties herein analyzed. Compounds 4, 5, 7, 10, 11, 13–15, 21, 22, 26, and 27 were isolated for the first time from A. espinosarum, despite this, the chemical content found in both varieties is consistent with that previously described. The flavanones, flavones and flavonols methoxy and dimethoxy derivatives are the chemophenetic markers of A. espinosarum. The structure of the known compounds was determined by spectroscopic and spectrometric techniques and their data compared with those previously reported. This is the first report of the isolation of compound 4, which was characterized as its 2,3,15-triacetyl (4A) and 2,15-diacetyl (4B) derivatives, whose spectroscopic and spectrometric data are described within.

Discovery of Cinnamylidene Derivative of Rhodanine with High Anthelmintic Activity against Rhabditis sp.

The treatment of parasitic infections requires the application of chemotherapy. In view of increasing resistance to currently in-use drugs, there is a constant need to search for new compounds with anthelmintic activity. A series of 16 cinnamylidene derivatives of rhodanine, including newly synthesized methoxy derivatives (1–11) and previously obtained chloro, nitro, and diethylamine derivatives (12–16), was investigated towards anthelmintic activity. Compounds (1–16) were evaluated against free-living nematodes of the genus Rhabditis sp. In the tested group of rhodanine derivatives, only compound 2 shows very high biological activity (LC50 = 0.93 µg/µL), which is higher than the reference drug albendazole (LC50 = 19.24 µg/µL). Crystal structures of two compounds, active 2 and inactive 4, were determined by the X-ray diffraction method to compare molecular geometry and search for differences responsible for observed biological activity/inactivity. Molecular modelling and selected physicochemical properties prediction were performed to assess the potential mechanism of action and applied in the search for an explanation as to why amongst all similar compounds only one is active. We can conclude that the tested compound 2 can be further investigated as a potential anthelmintic drug.

Benzoxazolone-arylpiperazinyl scaffold-based PET ligand for 5-HT7 : Synthesis and biological evaluation.

Efforts are underway to improve the diagnosis and treatment for neurological disorders like depression, anxiety, epilepsy, and schizophrenia. The G-protein-coupled receptors (GPCRs) 5-HT7 receptor, the most recently identified member of 5-HT receptor family dysregulation has an association with various central nervous system (CNS) disorders and its ligands have an edge as potential therapeutics. Here, we report the synthesis, characterization, and biological evaluation of diversely substituted methoxy derivatives of 2-benzoxazolone arylpiperazine for targeting 5-HT7 receptors. Out of all derivatives, only C-2 substituted derivative, 3-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)benzoxazol-2(3H)-one/ABO demonstrate a high affinity for human 5-HT7 receptors. [11 C]ABO was obtained by O-methylation of desmethyl-precursor using [11 C]CH3 OTf in the presence of NaOH giving a high radiochemical yield of 25 ± 12% (decay-corrected,n = 7) with stability up to 1.5 h postradiolabeling. In vitro autoradiography displays binding of [11 C]ABO in accordance with 5-HT7 distribution with a decrease of approximately 80% and 40% activity in the hippocampus and cerebellum brain region when administered with 10 µM cold ligand. Prefatory positron emission tomography scan results in Sprague-Dawley (SD) rat brain revealed fast and high radioactivity build-up in 5-HT7 receptor-rich regions, namely, the hippocampus (2.75 ± 0.16 SUV) and the cerebral cortex (2.27 ± 0.02 SUV) establishing selective targeting of [11 C]ABO. In summary, these pieces of data designate[11 C]ABO as a promising 5-HT7 receptor ligand that can have possible roles in clinics after its further optimization on different animal models.

Theoretical Insights on Improving Amidoxime Selectivity for Potential Uranium Extraction from Seawater.

Extraction of uranium from seawater is one of the important ways to solve the shortage of terrestrial uranium resources. Thereinto, the competition between uranyl and vanadium cations is a significant challenge in the commonly used amidoxime-based adsorbents for extracting uranium from seawater. An in-depth understanding of the extraction behaviors of modified amidoxime groups with uranyl and vanadium ions is one of the effective means to design and develop efficient adsorbents for selective uranium sequestration. In this work, we have designed and systematically investigated the alkyl and amino functionalized amidoxime, (Z)-2-amino-N'-hydroxy-N,N-dimethylbenzimidamide (L1), and its phenyl and methoxy derivatives ((Z)-3-amino-N'-hydroxy-N,N-dimethyl-2-naphthimidamide (L2) and (Z)-2-amino-N'-hydroxy-4-methoxy-N,N-dimethylbenzimidamide (L3)) by quantum chemistry calculations. In the uranyl complexes, the amidoxime groups prefer to act as η2-coordinated ligands as the amidoximes increase, and there exist substantial hydrogen bond interactions, which are different from the vanadium complexes. Various bonding analyses show that the L1 ligand possesses a stronger binding affinity to UO22+, and the -C6H5 and -CH3O substituent groups seem to have no effect on the improvement of extraction ability. Thermodynamic analysis confirms that the L1 ligand has a stronger extraction capability to uranyl ion compared to L2 and L3. According to the calculations of the vanadium (V) (VO2+ and VO3+) complexes with the L1 ligand, L1 is more likely to react with [H2VO4]- and [HVO4]2- to form VO2+ complexes. Expectantly, thermodynamic analysis displays a higher extraction capacity for uranyl ions than vanadium ions. Therefore, these alkyl and amino functionalized amidoxime ligands demonstrate high selectivity for uranyl over vanadium ions, which is mainly due to the coordination mode changes of these ligands toward vanadium in conjunction with the considerable hydrogen bonds in the uranyl complexes. These results are expected to afford useful clues for the design of efficient adsorbents for uranium extraction from seawater.

Non-Oxidative Photoreaction of 1,3,5-Triaryl-2-Pyrazoline-4-Ol (4-Methoxy) Derivatives

Non-Oxidative Photoreaction of 1,3,5-Triaryl-2-Pyrazoline-4-Ol (4-Methoxy) Derivatives

Cd2+-selective fluorescence response of TQEN (N,N,N',N'-tetrakis(2-quinolylmethyl)ethylenediamine) derivatives bearing ether oxygen-binding sites.

Moderate Zn2+ selectivity over Cd2+ (IZn/ICd = 1.6) in the fluorescence enhancement of TQEN (N,N,N',N'-tetrakis(2-quinolylmethyl)ethylenediamine) was changed to Cd2+ preference via the introduction of a methoxymethyloxy (MOMO) substituent at the 8-position of one of the four quinoline rings (IZn/ICd = 0.2). Thus, 8-MOMOTQEN (N-(8-methoxymethyloxy-2-quinolylmethyl)-N,N',N'-tris(2-quinolylmethyl)ethylenediamine) showed not only high Cd2+-selectivity but also an enhanced fluorescence quantum yield upon Cd2+ binding and high sensitivity for Cd2+ detection as shown by ϕCd = 0.065 and LOD (limit of detection) = 19 nM. The two oxygen atoms of the MOMO group in 8-MOMOTQEN play a crucial role in the fluorescent metal-ion selectivity because the corresponding hydroxy (8-OHTQEN) and methoxy (8-MeOTQEN) derivatives resulted in a poor fluorescent response and metal selectivity, respectively. Another N6O2 ligand, N,N'-bis(8-methoxy-2-quinolylethyl)-N,N'-bis(2-quinolylmethyl)ethylenediamine ((8-MeO)2TQEN) exhibited a Zn2+-selective fluorescence enhancement (IZn/ICd = 2.2), indicating the superiority of the MOMO group for the selective sensing of Cd2+.

Molecular photonics of dienones based on cycloalkanones and their derivatives

Spectroscopic, luminescent, and spectral kinetic properties of cycloalkanone-based dienones and their diethylamino, methylthio, methoxy, and dimethoxy derivatives were studied. The presence of electron-donating substituents results in a red shift of the absorption and fluorescence spectral maxima. A laser pulse causes dienones to undergo intersystem crossing to the underlying triplet state with a lifetime of 0.2–40 μs as well as results in the formation of stable photoproducts capable of photoinduced conversion to the initial dienones. It also gives rise to intermediate products resulting from redox photoreactions of 2,4-bis(4-diethylaminobenzylidene)cyclobutanone in methanol in the presence of electron donor (ascorbic acid) and acceptor (para-nitroacetophenone) compounds.

Isomeric bis(pyrazolyl)sulfones based on bis(1,1-dihydropolyfluoroalkyl)sulfones. A new type of ligands for metal-polymer complexes with silver cation

The work is devoted to the methods of synthesis of bis(polyfluoroalkenyl)sulfones and bis(polyfluoromethoxyalkenyl)sulfones as well as to the study of their reactions with diazomethane, resulting in the formation of N-methylated bis(pyrazolyl)sulfones isomers. Methods for the preparation of bis(polyfluoromethoxyalkenyl)sulfones not described previously in the literature have been developed by the addition of triethylamine and trimethylchlorosilane to a solution of the respective bis(polyfluoroalkyl)sulfones and methanol in diethyl ether in an argon atmosphere. A new method for the preparation of a previously unknown bis(3,3-difluoro-2,2-dimethoxypropyl)sulfone was suggested. The reaction occurs at room temperature in methanol in the presence of lithium hydroxide monohydrate. It was found that different regioisomeric bis(polyfluoroalkylpyrazolyl)sulfones are formed when using different methoxy derivatives of bis(polyfluoroalkenyl)sulfones in reaction with diazomethane, depending on the length of the polyfluoroalkyl moiety. These experimental data suggest that the attack of the double bond of methoxy-derived bis(polyfluoroalkenyl)sulfones by a molecule of diazomethane is influenced not only by the presence of an alkoxyl group, but also by the length of the polyfluoroalkyl substituent. The obtained bis(pyrazolyl)sulfones were investigated for the possibility of their use as ligands in the chemistry of metal complexes. It was shown that 5,5'-sulfonylbis[4-(difluoromethyl)-1-methyl-1H-pyrazole] forms a polymeric metal complex with silver nitrate. The results of X-ray structural analysis of the prepared coordination compound are presented. According to these results, the silver atom coordinates with two nitrogen atoms of pyrazole cycles of different molecules in the crystal of the obtained metal-complex compound, forming a supramolecular structure. In our opinion, an important role in this arrangement is played by the nitrate group that is coordinated with two silver atoms. As a result, we observed a supramolecular structure in the crystal that had a spiral structure with some free space in the middle. The paper also presents the results of spectral and X-ray diffraction analysis of a new regioisomeric compound of bis(3-hexafluoropropyl-1-methylpyrazolyl)sulfone.

Controlling the photoswitching of 2-(4′-diethylamino-2′-hydroxyphenyl)-1H-imidazo-[4,5-b]pyridine by pH

2-(4′-Diethylamino-2′-hydroxyphenyl)-1H-imidazo-[4,5-b]pyridine (DHP) has two mutually independent reaction paths, excited state intramolecular proton transfer (ESIPT) and twisted intramolecular charge transfer (TICT). To uncover the effect of acidity and basicity on the reaction coordinate, the molecule was studied in the complete range, from higher acidity H0 (Hammett’s acidity scale) – 10 to high basicity H_ (Yagil’s basicity scale) 16.4 using UV–visible and fluorescence techniques, along with quantum mechanical calculations. The molecule possesses complicated prototropic equibrium with multiple cations and anions in addition to the neutral species. The emission maximum changes from 375 nm to 560 nm depending on the acidity and basicity of the solution. All the prototropic species were identified experimentally and comprehensively entrenched with the help of computational calculations. The methoxy derivative was studied to substantiate the assignment. The neutral species predominantly emits the tautomer emission. Upon deprotonation one red shifted emission and one blue shifted emission are observed due to formation of two different monoanions. Even at higher basicity H_ 16.2, the dianion formation was not completed. Three monocations are formed, one emits normal emission, one emits tautomer emission and the third one emits highly Stokes shifted ICT emission. Among the dications, one dication undergoes biprotonic phototautomersism to produce tautomer of other dication in the excited state. Unlike dianion, the trication formation is completed at higher acidity H0 − 10.

Two methoxy derivatives of resveratrol, 3,3\u2032,4,5\u2032-tetramethoxy-trans-stilbene and 3,4\u2032,5-trimethoxy-trans-stilbene, suppress lipopolysaccharide-induced inflammation through inactivation of MAPK and NF-\u03baB pathways in RAW 264.7 cells

Background3,3′,4,5′-tetramethoxy-trans-stilbene (3,3′,4,5′-TMS) and 3,4′,5-trimethoxy-trans-stilbene (3,4′,5-TMS) are two methoxy derivatives of resveratrol. Previous researches have proved that resveratrol and its analogues have anti-inflammatory effect through suppressing mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. This study aims to study whether 3,3′,4,5′-TMS and 3,4′,5-TMS alleviate inflammation and the underlying mechanism.MethodsRAW 264.7 macrophage cells were treated with lipopolysaccharide (LPS) to induce inflammation and pretreated with 3,3′,4,5′-TMS or 3,4′,5-TMS. Cell viability was measured with the 3-(4,5)-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Nitric oxide (NO) release was detected by Griess reagent. The secretions of pro-inflammatory cytokines were assessed by ELISA kits. Protein expressions of signaling molecules were determined by Western blotting. Reactive oxygen species (ROS) production was detected by fluorescence staining and malondialdehyde (MDA) assay.Results3,3′,4,5′-TMS and 3,4′,5-TMS suppressed LPS-induced NO release and pro-inflammatory cytokines (IL-6 and TNF-α) secretions in a dose-dependent manner in RAW 264.7 cells. 3,3′,4,5′-TMS and 3,4′,5-TMS significantly down-regulated the LPS-induced expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), and partially suppressed the activation of MAPK (phosphorylation of p38, JNK, ERK), and NF-κB (phosphorylation of IKKα/β, p65 and IκBα) signaling pathways; where phosphorylation of ERK and p65 was mildly but not significantly decreased by 3,3′,4,5′-TMS. LPS-induced NF-κB/p65 nuclear translocation was inhibited by both 3,3′,4,5′-TMS and 3,4′,5-TMS. Moreover, both resveratrol derivatives decreased the ROS levels.Conclusions3,3′,4,5′-TMS and 3,4′,5-TMS significantly suppress LPS-induced inflammation in RAW 264.7 cells through inhibition of MAPK and NF-κB signaling pathways and also provide anti-oxidative effect. This study reveals potential therapeutic applications of 3,3′,4,5′-TMS and 3,4′,5-TMS for inflammatory diseases.

Synthesis of new methoxy derivatives of trans 2,3-diaryl-2,3-dihydrobenzofurans and evaluation of their anti-inflammatory activity

In the present study we synthesized new methoxy derivatives of trans 2,3-diaryl-2,3-dihydrobenzofurans, starting from suitable trans 2,3-diaryloxiranes, using regio- and stereoselective nucleophilic oxiranyl ring-opening reactions. The compounds were tested as anti-inflammatories in U937 cells. All compounds showed a significant role in inhibiting the NF-κB pathway and were able to restore normal ROS and NO level upon LPS activation. Moreover, regarding inhibition of ACLY, enantioenriched (50% ee) 7a50 showed more potency than the racemic counterpart 7arac, together with a higher reduction of prostaglandin E2 production, thus suggesting a stereoselective interaction in this pathway.

Discovery of New Pyrazolopyridine, Furopyridine, and Pyridine Derivatives as CDK2 Inhibitors: Design, Synthesis, Docking Studies, and Anti-Proliferative Activity.

New pyridine, pyrazoloyridine, and furopyridine derivatives substituted with naphthyl and thienyl moieties were designed and synthesized starting from 6-(naphthalen-2-yl)-2-oxo-4-(thiophen-2-yl)-1,2-dihydropyridine-3-carbonitrile (1). The chloro, methoxy, cholroacetoxy, imidazolyl, azide, and arylamino derivatives were prepared to obtain the pyridine-−C2 functionalized derivatives. The derived pyrazolpyridine-N-glycosides were synthesized via heterocyclization of the C2-thioxopyridine derivative followed by glycosylation using glucose and galactose. The furopyridine derivative 14 and the tricyclic pyrido[3′,2′:4,5]furo[3,2-d]pyrimidine 15 were prepared via heterocyclization of the ester derivative followed by a reaction with formamide. The newly synthesized compounds were evaluated for their ability to in vitro inhibit the CDK2 enzyme. In addition, the cytotoxicity of the compounds was tested against four different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549). The CDK2/cyclin A2 enzyme inhibitory results revealed that pyridone 1, 2-chloro-6-(naphthalen-2-yl)-4-(thiophen-2-yl)nicotinonitrile (4), 6-(naphthalen-2-yl)-4-(thiophen-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine (8), S-(3-cyano-6-(naphthaen-2-yl)-4-(thiophen-2-yl)pyridin-2-yl) 2-chloroethanethioate (11), and ethyl 3-amino-6-(naphthalen-2-yl)-4-(thiophen-2-yl)furo[2,3-b]pyridine-2-carboxylate (14) are among the most active inhibitors with IC50 values of 0.57, 0.24, 0.65, 0.50, and 0.93 µM, respectively, compared to roscovitine (IC50 0.394 μM). Most compounds showed significant inhibition on different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549) with IC50 ranges of 31.3–49.0, 19.3–55.5, 22.7–44.8, and 36.8–70.7 μM, respectively compared to doxorubicin (IC50 40.0, 64.8, 24.7 and 58.1 µM, respectively). Furthermore, a molecular docking study suggests that most of the target compounds have a similar binding mode as a reference compound in the active site of the CDK2 enzyme. The structural requirements controlling the CDK2 inhibitory activity were determined through the generation of a statistically significant 2D-QSAR model.

Biological Properties, Health Benefits and Enzymatic Modifications of Dietary Methoxylated Derivatives of Cinnamic Acid.

Methoxylated derivatives of cinnamic acid play an important role in the formation of the pro-health potential of food products. Numerous reports present them as molecules with strong antimicrobial, antidiabetic, anticancer as well as hepato-, cardio-, and neuroprotective activities. In the last three decades, many research groups have tried to extend the practical application of these molecules as therapeutic and antioxidant agents extensively studying the methods of their lipophilization as the solution of problems of their low oral bioavailability and rapid metabolism. This article summarizes the latest data of natural sources of occurrence, biological potential and bioavailability of methoxy derivatives of cinnamic acids. Metabolism and pharmacokinetics of this group of dietary compounds are also extensively discussed as well as reviewing the methods of their chemical and enzymatic lipophilization in the aspect of their use in food and pharmaceutical industries.