Methoxy Derivatives Research Articles

An efficient synthesis of flavanones and their docking studies with aldose reductase

A series of flavanone derivatives have been synthesized from 2-hydroxy acetophenone and benzaldehyde using fused calcium chloride in good to moderate yields, and their in vitro aldose reductase inhibitory activity has been tested on aldose reductase purified enzyme from Bovine lens. Most of the synthesized compounds exhibited potent aldose reductase inhibitory activity, and the obtained results are supported by the docking studies. Among the tested derivatives, 2, 3, 4-methoxy derivative 19 (IC50 5.88 ± 0.03 µM) exhibited the highest inhibitory activity whereas 2-methoxy derivative 12 showed the lowest, and the remaining compounds exhibited moderate activity with IC50 in the range of 6.09–7.89 µM. The spatial configuration of the most active derivative 19 was compared with pharmacophore requirements of the aldose reductase inhibitor site using a molecular modeling system.

Antilipolytic effects of 1,8-naphthyridine derivatives β-adrenoceptor antagonists in rat white adipocytes.

The rat fat cell β-adrenoceptors were investigated by studying the effects of new 1,8-naphthyridine derivatives synthesized starting from 7-amino-2-chloro-3-phenyl-1,8-naphthyridine on lipolysis induced by isoprenaline, and alprenolol. Lipolysis induced by isoprenaline agonist was competitively antagonized by the 1,8-naphthyridine analogue with a 7-hydroxy-2-(4'-methoxybenzylamine)-6-nitro-3-phenyl substituent designated as 3. In contrast, 10, 50, and 100μm of 7-methoxy and 7-ethoxy derivatives did not modify the concentration-response curve of isoprenaline. A rightward shift of the curve was, however, observed with 50μm of a 7-methoxy-2-(4'-methoxybenzylamine)-6-amino-3-phenyl substituent designated as 10. The selective β1 -AR antagonist, 7-hydroxy-4-morpholinomethyl-2-piperazino-1,8-naphthyridine slightly reduced isoprenaline-induced lipolysis only at high doses. Alprenolol-mediated lipolytic effect was antagonized by derivative 3, 10 and the selective β3 -AR antagonist SR 59,230A, but resistant to the selective β1 -AR antagonist 7-hydroxy-4-morpholinomethyl-2-piperazino-1,8-naphthyridine. The results provide preliminary pharmacological evidence for the antilipolytic effect of the newly synthesized 1,8-naphthyridine derivatives on rat fat cells. The analogues designated as 3 and 10 were the most potent antagonists of this series.

Ordered mesoporous silica functionalized with β-cyclodextrin derivative for stereoisomer separation of flavanones and flavanone glycosides by nano-liquid chromatography and capillary electrochromatography

In this paper a chiral stationary phase (CSP) was prepared by the immobilization of a β-CD derivative (3,5-dimethylphenylcarbamoylated β-CD) onto the surface of amino-functionalized spherical ordered mesoporous silica (denoted as SM) via a urea linkage using the Staudinger reaction. The CSP was packed into fused silica capillaries 100μm I.D. and evaluated by means of nano-liquid chromatography (nano-LC) and capillary electrochromatography (CEC) using model compounds for the enantio- and the diastereomeric separation. The compounds flavanone, 2′-hydroxyflavanone, 4′-hydroxyflavanone, 6-hydroxyflavanone, 4′-methoxyflavanone, 7-methoxyflavanone, hesperetin, hesperidin, naringenin, and naringin were studied using reversed and polar organic elution modes. Baseline stereoisomer resolution and good results in terms of peak efficiency and short analysis time of all studied flavonoids and flavanones glycosides were achieved in reversed phase mode, using as mobile phase a mixture of MeOH/H2O, 10mM ammonium acetate pH 4.5 at different ratios. For the polar organic mode using 100% of MeOH as mobile phase, the CSP showed better performances and the baseline chiral separation of several studied compounds occurred in an analysis time of less than 10min. Good results were also achieved by CEC employing two different mobile phases. The use of MeOH/H2O, 5mM ammonium acetate buffer pH 6.0 (90/10, v/v) was very effective for the chiral resolution of flavanone and its methoxy and hydroxy derivatives.

Partially fluorinated alkoxy groups − Conformational adaptors to changing environments

Lipophilicities of partially fluorinated n-propyloxy indole derivatives and their rates of oxidative metabolic degradation are presented. Comparison of the lipophilicity data with those of compounds containing the same partially fluorinated propyl groups attached to carbon or nitrogen reveals remarkable similarities and some distinct differences. A further striking difference in lipophilicity pattern is noted between terminally fluorinated n-propyloxy and corresponding methoxy derivatives. The lipophilicity patterns are rationalized in a consistent way by application of a simple rule-of-thumb based on polar-bond vector superposition, taking into account conformational aspects deduced from X-ray crystal structures and quantum chemical calculations. Several of these groups can switch between polar and non-polar conformations of comparable energies and may thus be regarded as potentially effective conformational adaptors to changing chemical environments. All compounds exhibit relatively high rates of metabolic degradation with a moderate correlation between degradation rate and lipophilicity.

The Missing Link in Leguminous Pterocarpan Biosynthesis is a Dirigent Domain-Containing Protein with Isoflavanol Dehydratase Activity.

Pterocarpan forms the basic structure of leguminous phytoalexins, and most of the isoflavonoid pathway genes encoding the enzymes responsible for its biosynthesis have been identified. However, the last step of pterocarpan biosynthesis is a ring closure reaction, and the enzyme that catalyzes this step, 2′-hydroxyisoflavanol 4,2′-dehydratase or pterocarpan synthase (PTS), remains as an unidentified ‘missing link’. This last ring formation is assumed to be the key step in determining the stereochemistry of pterocarpans, which plays a role in their antimicrobial activity. In this study, a cDNA clone encoding PTS from Glycyrrhiza echinata (GePTS1) was identified through functional expression fractionation screening of a cDNA library, which requires no sequence information, and orthologs from soybean (GmPTS1) and Lotus japonicus (LjPTS1) were also identified. These proteins were heterologously expressed in Escherichia coli and biochemically characterized. Surprisingly, the proteins were found to include amino acid motifs characteristic of dirigent proteins, some of which control stereospecific phenoxy radical coupling in lignan biosynthesis. The stereospecificity of substrates and products was examined using four substrate stereoisomers with hydroxy and methoxy derivatives at C-4′. The results showed that the 4R configuration was essential for the PTS reaction, and (−)- and (+)-pterocarpans were produced depending on the stereochemistry at C-3. In suspension-cultured soybean cells, levels of the GmPTS1 transcript increased temporarily prior to the peak in phytoalexin accumulation, strongly supporting the possible involvement of PTS in pterocarpan biosynthesis.

Spectral and luminescent properties of 2-(2-hydroxyphenyl)-5-(2,6-difluorophenyl)-1,3,4-oxadiazole and its methoxy and benzyloxy derivatives

Spectral and luminescent properties of 2-(2-hydroxyphenyl)-5-(2,6-difluorophenyl)-1,3,4-oxadiazole and its methoxy and benzyloxy derivatives

Resveratrol and its methoxy derivatives modulate the expression of estrogen metabolism enzymes in breast epithelial cells by AhR down-regulation.

Our earlier studies have shown that compared to resveratrol, its analogs with ortho-methoxy substituents exert stronger antiproliferative and proapoptotic activity. Since estrogens are considered the major risk factors of breast carcinogenesis, the aim of this study was to evaluate the effect of 3,4,2'-trimethoxy (3MS), 3,4,2',4'-tetramethoxy (4MS), and 3,4,2',4',6'-pentamethoxy (5MS) trans-stilbenes on the constitutive expression of the enzymes involved in estrogen metabolism, as well as receptors: AhR and HER2 in breast epithelial cell line MCF10A. The results showed different effect of resveratrol and its methoxy derivatives on the expression of genes encoding key enzymes of estrogen synthesis and catabolism. Resveratrol at the doses of 1 and 5µmol/L increased the level of CYP19 transcript and protein level, while 5MS reduced mRNA transcript of both CYP19 and STS genes. Resveratrol and all its derivatives reduced also SULT1E1 mRNA transcript level. The reduced expression of AhR, CYP1A1, and 1B1 was also found as a result of treatment with these compounds. The most significant changes were found in the case of AhR. The most potent inhibitor of CYP1A1 and 1B1 genes expression was 5MS, which reduced the levels of mRNA transcript and protein of both CYPs from 31 to 89% of the initial levels. These results indicate that methoxy derivatives of resveratrol might be efficient modulators of estrogen metabolism. Moreover, the number of methoxy groups introduced to stilbene structure may play a certain role in this effect.

Synthesis of Novel Indole-Benzimidazole Derivatives

2-Methylindole-3-acetic acid and its 5-methoxy derivative were prepared from the respective phenylhydrazines and levulinic acid. Indole-3-carboxylic acid was obtained from indole, dimethylformamide and trifluoroacetic acid. These indole carboxylic acids were then condensed with substituted o-phenylenediamines under high temperature conditions in the presence of polyphosphoric acid as a catalyst to give the combined indole-benzimidazoles.

ChemInform Abstract: Bioactive Constituents from Radermachera boniana.

Abstract17 Naphthalene‐based quinones are isolated from the roots of Radermachera boniana Dop.

Antioxidant properties, computational studies and corrosion inhibition potential of 3-hydroxy-1-(2-hydroxyphenyl)-5-(phenyl)-2,4-pentadien-1-one analogues

Ten derivatives of (2Z,4E)-3-hydroxy-1-(2-hydroxyphenyl)-5-phenylpenta-2,4-dien-1-one were investigated for their antioxidant properties and corrosion inhibition potential. The compounds were screened for their antioxidant activity using the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging assay and the ferric reducing antioxidant power (FRAP) assay. The methoxylated analogues generally showed better antioxidant activity than the fluorinated analogues. The compounds were screened for drug-likeness properties using in silico techniques. They were found to obey the Lipinski rule of five, which indicated promising absorption or permeability properties through biological membranes. The flexible-ligand docking studies were performed using Auto Dock 4.2 with protein tyrosinase (PDB code: 3NM8). Furthermore, the methoxy derivatives exhibited relatively high binding energies, indicating the possibility of greater interactions with proteins. The compounds were also tested for possible anticorrosion properties using the potentiodynamic polarization and electrochemical impedance spectroscopy techniques. All the compounds showed appreciable corrosion inhibition efficiency for mild steel in 1M HCl. These compounds are mixed-type inhibitors. The adsorption of the compounds on a mild steel surface obeyed the Temkin adsorption isotherm and the derived adsorption thermodynamic parameters indicate a spontaneous and chemical adsorption process.

6-Methoxy-indanone derivatives as potential probes for β-amyloid plaques in Alzheimer's disease

A series of 6-methoxy indanone derivatives was synthesized and evaluated as potential probes for β-amyloid plaque imaging in Alzheimer's disease (AD). Two derivatives (5d and 5k) displayed significant binding abilities in fluorescent staining experiments using the brain sections of AD patients. Two derivatives showed high binding affinities to β-amyloid aggregates (5j, Ki = 5.82 ± 0.19 nM) and brain homogenates of AD patients (5j, Ki = 18.96 ± 0.28 nM) in in vitro binding assay. With a log P value of 3.45, [125I]5k exhibited an excellent initial brain uptake (5.29%ID g−1, 2 min after i.v.) and a fast clearance from the brain in biodistribution experiments in normal mice. In autoradiography, [125I]5k exhibited an obvious binding ability to β-amyloid plaques and a relatively low nonspecific binding in the brain sections of AD patients (in vitro) and APP/PS1 transgenic mice (in vitro and ex vivo). Results suggest that 5k is a potential probe for detecting β-amyloid plaques in vivo.

Polybrominated Diphenyl Ethers: Structure Determination and Trends in Antibacterial Activity.

Antibacterial-guided fractionation of the Dictyoceratid sponges Lamellodysidea sp. and two samples of Dysidea granulosa yielded 14 polybrominated, diphenyl ethers including one new methoxy-containing compound (8). Their structures were elucidated by interpretation of spectroscopic data of the natural product and their methoxy derivatives. Most of the compounds showed strong antimicrobial activity with low- to sub-microgram mL(-1) minimum inhibitory concentrations against drug-susceptible and drug-resistant strains of Staphylococcus aureus and Enterococcus faecium, and two compounds inhibited Escherichia coli in a structure-dependent manner.

Synthesis and SAR studies of potent H+/K+-ATPase inhibitors of quinazolinone-Schiff’s base analogues

A series of quinazolinone derived Schiff base derivatives 7–36 were synthesized and characterized by analytical and spectroscopic techniques. The synthesized analogues were screened for their in vitro H+/K+-ATPase inhibition. Most of the compounds showed excellent activity, compared to that of omeprazole, a reference drug. In particular, hydroxy and methoxy derivatives 13–24 were the most active compounds possessing a significant increase for different substituents on the benzene ring thus, contributing positively to gastric H+/K+-ATPase inhibition. Preliminary structure-activity relationship revealed that the compounds 13–24 with electron donating moiety (OH, OCH3) were found to be excellent activity and compounds 9–12 and 25–36 with electron withdrawing moiety (Cl, F, NO2 and Br) were found to be least antiulcer agents.

Sesquiterpene Hydroquinones with Protein Tyrosine Phosphatase 1B Inhibitory Activities from a Dysidea sp. Marine Sponge Collected in Okinawa.

Three new sesquiterpene hydroquinones, avapyran (1), 17-O-acetylavarol (2), and 17-O-acetylneoavarol (3), were isolated from a Dysidea sp. marine sponge collected in Okinawa together with five known congeners: avarol (4), neoavarol (5), 20-O-acetylavarol (6), 20-O-acetylneoavarol (7), and 3'-aminoavarone (8). The structures of 1-3 were assigned on the basis of their spectroscopic data. Compounds 1-3 inhibited the activity of protein tyrosine phosphatase 1B with IC50 values of 11, 9.5, and 6.5 μM, respectively, while known compounds 4-8 gave IC50 values of 12, >32, 10, 8.6, and 18 μM, respectively. In a preliminary investigation on structure-activity relationships, six ester and methoxy derivatives (9-14) were prepared from 4 and 5.

Bioactive Constituents from Radermachera boniana.

AbstractThe bioassay‐directed fractionation of the roots of Radermachera boniana Dop. (Bignoniaceae) led to the isolation of 17 naphthalene‐based quinones and related derivatives including the new radermacherones A (1), B (2) and C (6), radermaquinone (3), and radermacherol (5). The absolute configuration of 2 was determined through X‐ray crystallographic analysis. The isolates 3, hydroxy‐β‐isonaphthoquinone (4), 6, α‐naphthoquinone (8), β‐naphthoquinone (9), 3‐hydroxy‐β‐naphthoquinone (10), 4‐oxo‐β‐naphthoquinone (11), 2‐acetyl‐naphtha[2,3‐b]furan‐4,9‐dione (BBI608) (12), 2‐acetyl‐7‐methoxy‐naphtho[2,3‐b]furan‐4,9‐dione(13), stenocarpoquin‐one B (14), dehydro‐α‐isonaphthoquinone (15) and 3‐hydroxydehydro‐α‐isonaphthoquinone (16) showed cytotoxic activity in a cancer cell line panel comprising KB, Col‐2, Lu‐1 and MCF‐7 with IC50 values ranging from 0.15‐38.6 µM. Compounds 12 (known as BBI608) and its methoxy derivative, 13 with extended conjugation showed the highest cytotoxicity among the tested compounds with IC50 values ranging from 0.12‐3.33 µM, but 13 showed much different cancer cell killing selectivity than 12.

Pheochromocytoma and Neurofibromatosis Type 1: An Exceptional Association

The association of a pheochromocytoma to a neurofibromatosis type 1 is a rare association. We relate the observation of a 62 years female patient who had, sinced a young age, showed cafe au lait spots and neurofibromas on the entire body, and been monitored for the last 4 years for high blood pressure with headaches, excessive sweating and palpitations. Dosage of urine catecholamine metabolites has revealed a rate elevated to 20 times the normal. Adrenal tomodensitometry has revealed a voluminous heterogeneous mass occupying the right adrenal loge, presenting a narrow contact with the inferior vena cava, and with the upper pole of the right kidney, measuring 10.5 x 9.3 x 8.7 cm, along with a small heterogeneous mass of the left adrenal. Under the scope of the neurofibromatosis, fundus photography has been performed and showed Lisch nodules, while cerebral tomodensitometry results were normal. After undergoing bilateral andrenalectomy, anatomopathological examination has revealed a completely excised pheochromocytoma on the right adrenal, and a macro-nodular adrenal hyperplasia on the left adrenal. Metaiodobenzylguanidine scan has not showed any ectopic placement of the pheochromocytoma, and urinary methoxy derivatives were normal post-surgery. Screening and adequate surgical support of the pheochromocytoma, for patients with neurofibromatosis type 1 presenting high blood pressure, allows to avoid complications.

The Dependence of Mesomorphism on the Terminal Group

A novel azoester homologous series of liquid crystals (LCs) was synthesized and studied with a view to understanding and establishing the effect of molecular structure on LC behavior. The series consists of twelve members. All the members of the series exhibit a nematogenic mesophase. The methoxy and propyloxy derivatives are monotropic and the rest of the homologs are enantiotropic nematogenic. Smectic mesophase formation is completely absent. Transition temperatures and the textures of the nematic phase were observed and determined through an optical polarizing microscope equipped with a heating stage. Transition curves (Cr‒N and N‒I) of a phase diagram behave in a normal manner except for the hexadecyloxy homolog which deviates from normal behavior in the N‒I transition curve. The N‒I transition curve exhibits an odd-even effect. The textures of the nematic phase are threaded or Schlieren in type. The average thermal stability for the nematic phase is 158°C. The nematogenic mesophase length ranges from 27°C to 226°C. The analytical and spectral data confirms the molecular structures of the homologs. The LC properties of the presently investigated novel series are compared with a structurally similar known series. The novel azoester series is entirely nematogenic without exhibition of smectogenic character.

Artemisia spicigera Essential Oil: Assessment of Phytochemical and Antioxidant Properties

Abstract Background: Essential oils (EO), also called volatile odoriferous oil, are aromatic oily liquids extracted from different parts of plants. In general, the constituents in EOs are terpenes, aromatic compounds (aldehyde, alcohol, phenol, methoxy derivatives, and so on), and terpenoids (isoprenoids). Essential Oils have been known to possess antioxidant and antimicrobial activities, thereby serving as natural additives in foods and food products. Objectives: The aim of this study was to assess the quantity and quality of compounds, with active chemical and antioxidant properties, of Artemisia spicigera essential oil (EO) due to the effect of geographic location and season of harvest on the phenolic compounds of the plant. The plant was collected from east Azarbayjan province, Iran (both before and after the flowering stage). Materials and Methods: A. spicigera EO was analyzed by gas chromatogram/mass spectrometry (GC-MS). The antioxidant activity and total phenolic content before and after flowering were evaluated by the Folin Ciocalteu method. Also, the yields of essential oil as a percentage based on the level of dry plant and the volume of extracted oil was determined. Results: Analysis of A. spicigera EO by gas chromatogram-mass spectrometry showed that spachulenol 1 H cycloprop (18.39%) and bicyclo hexan-3-en, 4-met (26.16%), were the prominent EOs of Artemisia before and after the flowering stage; the total phenolic EO before and after the flowering stage was 23.61 ± 1.08 μg/mL and 17.71 ± 0.9 μg/mL, respectively. Also level of flavonoid content before and after the flowering stage was 37.27 ± 1.70 μg/mL and 29.04 ± 1.30 μg/mL, respectively. This EO was able to reduce the stable free radical 2, 2-diphenol,1-picryl hydrazyl (DPPH) with an IC50 of 86.14 ± 2.23 and 96.18 ± 2.61 μg/mL, before and after flowering, respectively. Yield of EO before and after flowering was 0.5% and 0.6%, respectively. Conclusions: Results have shown that A. spicigera EO before and after flowering has antioxidant properties and therefore can be used in combination with other preservatives to protect food materials against a variety of oxidative systems. Keywords: Essential Oils, Antioxidants, Gas Chromatography, Artemisia spicigera

Functionalization of the benzobicyclo[3.2.1] octadiene skeleton possessing one isolated double bond via photocatalytic oxygenation

Photocatalytic oxygenation of three phenyl derivatives of a bicyclic skeleton with a free double bond 1a, 1b and 1c were carried out by utilizing a cationic and an anionic manganese(III) porphyrin irradiated in the visible range. While photocatalysis of 1a and 1b led to the formation of the corresponding hydroperoxy derivatives 2 and 3, respectively, (besides unidentified high-molecular-weight products) in the presence of the anionic Mn(III) porphyrin, the cationic photocatalyst proved to be less efficient and less selective with 1a. In the case of 1b, also with the cationic porphyrin, the corresponding hydroperoxy derivative (3) was the main product at a shorter reaction time (2 h), whereas a longer irradiation (4 h) led to the significant formation of a keto derivative (5) with a hydroperoxy substituent and a free double bond at positions deviating from those in the previous products (2 and 3). A dramatic change in the reactivity was observed for the methoxy derivative (1c). It gave only traces of identifiable products by using the anionic photocatalyst, while application of the cationic Mn(III) porphyrin resulted in a relatively efficient formation of an epoxy derivative (6) due to the reaction of the isolated double bond.

Synthesis, Biological Activity of Pyrimidine Linked with Morpholinophenyl Derivatives

A new series of 5‐fluoro‐N4‐(3‐(4‐substitutedbenzylamino)phenyl)‐N2‐(4‐morpholinophenyl)pyrimidine‐2,4‐diamine derivatives (7a, 7b, 7c, 7d, 7e, 7f, 7g, 7h, 7i, 7j) are prepared from using an intermediate compound 5‐fluoro‐N4‐(3‐(aminophenyl)‐N2‐(4‐morpholinophenyl)pyrimidine‐2,4‐diamine (5). The structures of the newly synthesized products are established from their spectral 1H‐NMR, 13C‐NMR, 19F‐NMR, ESI‐MS, and analytical data. Here we report the synthesized compounds and larvicidal activity. All the compounds are screened for their significant larvicidal activity against third instar larvae at 24, 48, and 78‐h time exposure, and values were compared with standard drug Malathion. The Compounds 7i, 7a, 7c, 7f, and 7j exhibited significant activity. However the compounds 7b, 7e, 7d, and 7h showed excellent activity when compared to the above compounds and to standard drug malathion too because of the presence of mild electron withdrawing groups such as trifluoro, fluorine, hydroxy, nitro, and methoxy derivatives which are attached to the benzyl ring.