Benzoic Acid Methyl Ester Research Articles

Variation in the Aroma Composition of Jasmine Tea with Storage Duration.

This study investigated the changes in the aroma of jasmine tea during storage. Solid-phase micro-extraction (SPME)-gas chromatography (GC)-mass spectrometry (MS) and stir bar sorptive extraction (SBSE)-GC-MS were combined to detect all volatile compounds. GC-olfactometry (GC-O), odor activity value (OAV), and p-value were employed to analyze and identify the key aroma compounds in six jasmine tea samples stored for different durations. Nine key aroma compounds were discovered, namely (Z)-3-hexen-1-yl acetate, methyl anthranilate, methyl salicylate, trans-β-ionone, linalool, geraniol, (Z)-4-heptenal, benzoic acid methyl ester, and benzoic acid ethyl ester. The importance of these compounds was confirmed through the aroma addition experiment. Correlation analysis showed that (Z)-4-heptenal might be the main reason for the increase in the stale aroma of jasmine tea. Through sensory evaluation and specific experimental analysis, it can be concluded that jasmine tea had the best aroma after 3 years of storage, and too long a storage time may cause the overall aroma of the tea to weaken and produce an undesirable odor. The findings can provide a reference for the change in aroma during the storage of jasmine tea and provide the best storage time (3 years) in terms of jasmine tea aroma.

Phytochemical Screening of Rhizome Extract of Curcuma longa Linn. Grown in Bangladesh through GC-MS and its Bioactivities

The methanolic extract of Curcuma longa L. rhizome was subjected to Gas Chromatography-Mass Spectrometric (GC-MS) analysis. The chromatographic investigation of the extract showed 27 constituents of which 19 compounds were newly found from C. longa. Here, the peaks obtained in the total ion chromatogram were compared with the National Institute of Standards and Technology (NIST) database for identification of the constituents. The most plentiful component was 9-octadecenamide (Z) (5.93%). The component present in the lowest amount was 4-hydroxy-3-methoxy benzoic acid methyl ester (0.08%). The rhizome extract of C. longa and its six fractions (F1-F6) obtained through vacuum liquid chromatography (VLC) were also investigated for antioxidant, cytotoxic and antimicrobial activities.The crude extract and its fractions (F4-F6) exhibited strong antioxidant activity having IC50 values of 19.85, 18.41, 26.72 and 16.79 μg/ml, respectively compared to the standards butylated hydroxyl anisole (IC50 = 11.42 μg/ml) and ascorbic acid (IC50 = 9.01 μg/ml). Strong cytotoxicity was found in crude extract (LC50 = 1.81 μg/ml) and fractions F4 (LC50 = 2.4 μg/ml), F5 (LC50 = 2.5 μg/ml) and F6 (LC50 = 2.3 μg/ml) when compared to the standard, tamoxifen (LC50 = 0.13 μg/ml). Fractions F1-F3 displayed mild to moderate antibacterial activity against Bacillus megaterium, Staphylococcus aureus and Pseudomonas aeruginosa in comparison with the standard, Kanamycin. The compounds obtained through GC-MS may explain the above activities. The present results showed the prospect of this medicinal plant to explore further to determine the bioactive components. Dhaka Univ. J. Pharm. Sci. 22(1): 11-20, 2023 (June)

Synthesis, Crystal Structure, DFT Calculations, Hirshfeld Surface Analysis and In Silico Drug-Target Profiling of (R)-2-(2-(1,3-Dioxoisoindolin-2-yl)propanamido)benzoic Acid Methyl Ester.

The work here reflects synthesis, DFT studies, Hirshfeld charge analysis and crystal data exploration of pharmacologically important (R)-2-(2-(1,3-dioxoisoindolin-2-yl)propanamido)benzoic acid methyl ester (5) to understand its properties for further chemical transformations. The methyl anthranilate (2) was produced by the esterification of anthranilic acid in an acidic medium. The phthaloyl-protected alanine (4) was rendered by the fusion of alanine with phthalic anhydride at 150 °C, followed by coupling with (2) furnished isoindole (5). The characterization of products was performed using IR, UV-Vis, NMR and MS. Single-crystal XRD also verified the structure of (5) in which N-H⋯O bonding stabilizes the molecular configuration of (5), resulting in the formation of S(6) hydrogen-bonded loop. The molecules of isoindole (5) are connected in the form of dimers, and the π⋯π stacking interaction between aromatic rings further stabilizes the crystal packing. DFT studies suggest that HOMO is over the substituted aromatic ring, the LUMO is present mainly over the indole side, and nucleophilic and electrophilic corners point out the reactivity of the product (5). In vitro and in silico analysis of (5) shows its potential as an antibacterial agent targeting DNA gyrase and Dihydroorotase from E. coli and tyrosyl-tRNA synthetase and DNA gyrase from Staphylococcus aureus.

Nitrilase mediated mild hydrolysis of a carbon-14 nitrile for the radiosynthesis of 4-(7-hydroxycarbamoyl-[1-14 C-heptanoyl]-oxy)-benzoic acid methyl ester, [14 C]-SHP-141: A novel class I/II histone deacetylase (HDAC) inhibitor.

A strategy has been developed for the carbon-14 radiosynthesis of [14 C]-SHP-141, a 4-(7-hydroxycarbamoyl-heptanoyloxy)-benzoic acid methyl ester derivative containing a terminal hydroxamic acid. The synthesis involved four radiochemical transformations. The key step in the radiosynthesis was the conversion of the 7-[14 C]-cyano-heptanoic acid benzyloxyamide [14 C]-4 directly into the carboxylic acid derivative, 7-benzyloxycarbamoyl-[14 C]-heptanoic acid [14 C]-8 using nitrilase-113 biocatalyst. The final step involved deprotection of the benzyloxy group using catalytic hydrogenation to facilitate the release of the hydroxamic acid without cleaving the phenoxy ester. [14 C]-SHP-141 was isolated with a radiochemical purity of 90% and a specific activity of 190 μCi/mg from four radiochemical steps starting from potassium [14 C]-cyanide in a radiochemical yield of 45%.

A novel derivative of Genistein inhibits proliferation of ovarian cancer HO-8910 cells by regulating reactive oxygen species*

Abstract Objective To investigate the anticancer effect of a novel derivative of genistein (5-hydroxy-4′-nitro-7-propionyloxy-genistein, HNPG) on human ovarian cancer HO-8910 cells and its possible molecular mechanism. Methods HO-8910 cells were cultured in vitro, and the inhibitory effect of HNPG on proliferation was determined using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The effect of HNPG on inducing apoptosis was examined using FCM with Annexin V-FITC and propidium iodide staining. The effect of HNPG on regulating reactive oxygen species (ROS) was measured using FCM with 2′,7′-di chlorodihydro-fluorescein diacetate staining. The effect of HNPG on modulating mitochondrial membrane potential (MMP) was determined using FCM with lipophilic cationic dye 2 (6 Amino 3 imino 3H xanthen 9 yl) benzoic acid methyl ester (Rh123) staining. The bioactivity of superoxide dismutase (SOD) and catalase (CAT) and the content of glutathione (GSH) and malondialdehyde (MDA) were detected using enzyme-linked immunosorbent assay. The related apoptotic proteins, including bcl-2, bax, cyt-c, and cleaved-caspase-3, were assessed using western blotting. Results HNPG exhibited dramatic antitumor activity against HO-8910 cells in vitro, inhibited proliferation, and induced apoptosis in a time- and dose-dependent manner. These effects were accompanied by reduced bioactivity of SOD and CAT, reduced GSH content, and enhanced MDA content. Simultaneously, the amount of ROS was increased and the level of MMP was reduced, along with upregulation of mitochondrial apoptosis pathway-related proteins, bax, cyt-c, and cleaved-caspase-3; bcl-2 protein was downregulated. Conclusion HNPG inhibited proliferation of human ovarian cancer HO-8910 cells in vitro, which might be related to decreased bioactivity of SOD and CAT. HNPG also reduced GSH content, which resulted in ROS accumulation in cells, damaged the integrity of mitochondrial membrane, and induced cell apoptosis.

A determination of the aerosolization efficiency of drugs of abuse in a eutectic mixture with nicotine in electronic cigarettes

Characterize the effects of drug interactions with nicotine in the electronic cigarette (e-cigarette). E-liquids are composed of vegetable glycerin (VG), propylene glycol (PG), an active ingredient such as nicotine, and flavorings (Mulder, H.A., et al., Sci Rep., 2019, 9, 102201). Users can adulterate e-liquids with other pharmacologically active substances (Varlet, V. Toxics, 2016, 4, 29). The interaction between the diluent and nicotine forms a eutectic mixture, reducing the melting point to a temperature lower than the individual compounds and promoting aerosolization of the drugs (Gala, U., et al. J Dev Drugs., 2013, 2, e130). The purpose of this study was to evaluate the effect of nicotine on the aerosolization efficiency and recovery of methadone and cocaine using an aerosol capture method adopted from the established Cooperation Centre for the Scientific Research Relative to Tobacco (CORESTA) E-cigarette Task Force industry method. Individual e-liquids were prepared with 12 mg/mL nicotine, methadone, and cocaine in 1:1 PG:VG and drug-free. Aerosol capture was performed using parameters adopted from the CORESTA method. The puff profile was an inhale duration of 3 seconds, an exhale duration of 10 seconds, and a puff volume of 60 mL for a total of 15 puffs. A method for quantitation was validated on a Gas Chromatograph-Mass Spectrometer over five days. The linear range for nicotine was determined to be 500–20,000 ng/mL. Bias and precision were evaluated using quality controls prepared at 1500, 8000, and 16,000 ng/mL. The linear range for methadone and cocaine was 50–5000 ng/mL. Bias and precision were evaluated using quality controls prepared at 150, 1500, and 4000 ng/mL. Carryover was determined for all compounds by evaluating a blank after the injection of the highest calibrator. Aerosol samples were analyzed for drug recovery and dose. Samples were also evaluated for the pyrolytic products of nicotine, methadone, and cocaine: β-nicotyrine (nicotine), EDDP (methadone), and benzoic acid and anhydroecgonine methyl ester (cocaine). The average linear regression ( n = 5) for nicotine, methadone, and cocaine had an r2 > 0.996. Bias and precision for all analytes were within ± 9% and ± 12%CV, respectively. No carryover was observed. In the single drug e-liquids prepared at 12 mg/mL ( n = 3), 1.6 ± 0.2 mg of nicotine, 2.7 ± 0.1 mg of methadone, and 0.94 ± 0.04 mg of cocaine were aerosolized. In the nicotine/methadone mixture ( n = 3), nicotine and methadone increased to 3.7 ± 0.5 mg and 3.7 ± 0.1 mg, respectively. In the nicotine/cocaine mixture ( n = 3), nicotine and cocaine increased to 5.7 ± 2 mg and 2.7 ± 0.2 mg, respectively. In the 15 puffs of the nicotine, methadone, and cocaine e-liquids, 0.22 ± 0.02 g, 0.31 ± 0.01 g, and 0.15 ± 0.02 g ( n = 3) were aerosolized, respectively. In the nicotine/methadone mixture, 0.37 ± 0.01 g ( n = 3) of e-liquid was aerosolized. In the nicotine/cocaine mixture, 0.38 ± 0.02 g ( n = 3) was aerosolized. Pyrolytic products were identified in the e-liquids and aerosol samples, and therefore were not a result of aerosolization. E-liquids containing nicotine and other drugs create a eutectic mixture and can increase the amount of drug delivered in the aerosol. Increases in dose from combining drugs in an e-liquid may result in adverse reactions. The formation of pyrolytic products did not impact the aerosolization efficiency of the parent drugs; however, their presence may cause unexpected effects. The eutectic mixture can result in an increase in aerosolized drug doses.

Cytotoxic Phenylpropanoid Derivatives and Alkaloids from the Flowers of Pancratium maritimum L.

Regarding our growing interest in identifying biologically active leads from Amaryllidaceous plants, the flowers of Pancratium maritimum L. (Amaryllidaceae) were investigated. Purification of the cytotoxic fractions of the alcoholic extract of the flowers gave a new glycoside, 3-[4-(β-D-glucopyranosyloxy)phenyl]-2-(Z)-propenoic acid methyl ester (1), together with the previously reported compounds 3-methoxy-4-(β-D-glucopyranosyloxy)benzoic acid methyl ester (2), 3-(4-methoxyphenyl)propan-1-ol-1-O-β-D-glucopyranoside (3), (E)-3-(4-hydroxyphenyl)acrylic acid methyl ester (4), caffeic acid (5), dihydrocaffeic acid methyl ester (6), and pancratistatin (7). Interestingly, compounds 1 and 2 are phenolic-O-glycosides, while the glucose moiety in 3 is attached to the propanol side chain. This is the first report about the existence of 1–6 in the genus Pancratium. Further, glycosides 1–3 from the Amaryllidaceae family are reported on here for the first time. The structures of 1–7 were determined by analyses of their 1D (1H and 13C) and 2D (COSY, HMQC, HMBC) NMR spectra, and by high-resolution mass spectral measurements. Pancratistatin displayed potent and selective growth inhibitory effects against MDA-MB-231, HeLa, and HCT 116 cells with an IC50 value down to 0.058 µM, while it possessed lower selectivity towards the normal human dermal fibroblasts with IC50 of 6.6 µM.

Pilot Study on Exhaled Breath Analysis for a Healthy Adult Population in Hawaii.

Fast diagnostic results using breath analysis are an anticipated possibility for disease diagnosis or general health screenings. Tests that do not require sending specimens to medical laboratories possess capabilities to speed patient diagnosis and protect both patient and healthcare staff from unnecessary prolonged exposure. The objective of this work was to develop testing procedures on an initial healthy subject cohort in Hawaii to act as a range-finding pilot study for characterizing the baseline of exhaled breath prior to further research. Using comprehensive two-dimensional gas chromatography (GC×GC), this study analyzed exhaled breath from a healthy adult population in Hawaii to profile the range of different volatile organic compounds (VOCs) and survey Hawaii-specific differences. The most consistently reported compounds in the breath profile of individuals were acetic acid, dimethoxymethane, benzoic acid methyl ester, and n-hexane. In comparison to other breathprinting studies, the list of compounds discovered was representative of control cohorts. This must be considered when implementing proposed breath diagnostics in new locations with increased interpersonal variation due to diversity. Further studies on larger numbers of subjects over longer periods of time will provide additional foundational data on baseline breath VOC profiles of control populations for comparison to disease-positive cohorts.

Establishment of salicylic acid derived silylation reagents for protection of alcohols

In this work, we describe salicylic acid derived 2-[(trimethylsilyl)oxy]-benzoic acid methyl ester (TMSSME) and its TBDMS- (TBDMSSME) and TIPS-analogous (TIPSSME) as novel silylation reagents to furnish silyl ethers from alcohols. Silylation readily occurred in yields of 55–97% with TMSSME for a variety of aliphatic and aromatic alcohols. The reaction was effectively catalyzed by Dowex (50Wx8) under mild reaction conditions. Silylation with the corresponding TBDMS- and TIPS-reagents, however, required modified reaction conditions and only occurred on primary alcohols in good yields

The effect of isolates from Cassipourea flanaganii (Schinz) alston, a plant used as a skin lightning agent, on melanin production and tyrosinase inhibition

Ethnopharmacological relevanceThe Zulu and Xhosa people of South Africa use the stem bark of Cassipourea flanaganii as a skin-lightning cosmetic. Aim of the studyTo isolate and identify compounds responsible for the skin lightning properties from the stem bark of Cassipourea flanaganii and to evaluate their cytotoxicity towards skin cells. Materials and methodsExtracts from the stem bark of Cassipourea flanaganii were isolated using chromatographic methods and structures were determined using NMR, IR and MS analysis. The tyrosinase inhibitory activity and the ability to inhibit the production of melanin were determined using human primary epidermal melanocyte cells. Cytoxicity was established using the same melanocytes and a neutral red assay. ResultsOne previously undescribed compound, ent-atis-16-en-19-al (1) along with the known ent-atis-16-en-19-oic acid (2), ent-atis-16-en-19-ol (3), ent-kaur-16-en-19-oic acid (4), ent-kaur-16-en-19-al (5), ent-manoyl oxide (6), guinesine A (7), guinesine B (8), guinesine C (9), lichenxanthone (10), 2,4-dihydroxy-3,6-dimethyl benzoic acid methyl ester (11), lynoside (12), lupeol (13), β-amyrin (14), docosyl ferulate (15), stigmasterol, sitosterol and sitosterol-O-glucoside were isolated in this investigation. An impure fraction containing compound 3 was acetylated to obtain 19-acetoxy-ent-atis-16-ene (3a). Compounds 10 and 11 are usually isolated from lichen, hence they are possible contaminants of lichen harvested with the bark. Compounds 1, 3a, 5–14 were not significantly cytotoxic to the primary epidermal melanocyte cells (P > 0.05) when compared to the negative and positive controls (DMSO, 0.1% and hydrogen peroxide, 30 wt% in water). Inhibition of tyrosinase was significantly greater with respect to the negative control (P < 0.001) for compounds 3a, 5–8 and 9–10 at 10 μM and for compounds 5–8 and 9–10 at 100 μM. Compared to hydroquinone (the positive control) at 10 μM, the level of inhibition was comparable or to that of compounds 3a, 5, 6, and 8–10 at 10 μM, with 9 and 10 showing a greater level of inhibition. Inhibition of melanin was both concentration and time dependent for all compounds tested with higher melanin content at 24 h compared to 48 h s and at 10 mM compared to100 mM at both time points; melanin content was significantly lower for hydroquinone at both time points and concentrations. ConclusionsCompounds 1, 5–14, isolated from Cassipourea flanaganii and the derivative 3a showed low cytotoxicity. All compounds had a clear time and concentration dependent effect on melanin content which did not appear to be dependent on their inhibition of tyrosinase.

A 3D Heterotypic Breast Cancer Model Demonstrates a Role for Mesenchymal Stem Cells in Driving a Proliferative and Invasive Phenotype.

Previous indirect 2D co-culture studies have demonstrated that mesenchymal stem cells (MSCs) promote breast cancer (BC) progression through secretion of paracrine factors including growth factors, cytokines and chemokines. In order to investigate this aspect of the tumour microenvironment in a more relevant 3D co-culture model, spheroids incorporating breast cancer cells (BCCs), both cell lines and primary BCCs expanded as patient-derived xenografts, and MSCs were established. MSCs in co-cultures were shown to enhance proliferation of estrogen receptor (ER)/progesterone receptor (PR)-positive BCCs. In addition, co-culture resulted in downregulation of E-cadherin in parallel with upregulation of the epithelial-mesenchymal transition (EMT)-relation transcription factor, SNAIL. Cytoplasmic relocalization of ski-related novel protein N (SnON), a negative regulator of transforming growth factor-beta (TGF-β) signalling, and of β-catenin, involved in a number of pathways including Wnt signalling, was also observed in BCCs in co-cultures in contrast to monocultures. In addition, the β-catenin inhibitor, 3-[[(4-methylphenyl)sulfonyl]amino]-benzoic acid methyl ester (MSAB), mediated reduced growth and invasion in the co-cultures. This study highlights the potential role for SnON as a biomarker for BC invasiveness, and the importance of interactions between TGF-β and Wnt signalling, involving SnON. Such pathways may contribute towards identifying possible targets for therapeutic intervention in BC patients.

Arylsulfonamides From the Roots and Rhizomes of Tupistra chinensis Baker

One new arylsulfonamide (1) and a novel natural product (2) were isolated from the roots and rhizomes of Tupistra chinensis Baker. Their structures were characterized by physicochemical properties and spectroscopic methods, as 2-[2-([1,1′-biphenyl]-4-ylsulfonylamino)-benzoylamino]-benzoic acid methyl ester (1), 2-[([1,1′-biphenyl]-4-ylsulfonyl)amino]-benzoic acid (2), respectively. Additionally, the cytotoxic activity of 1-2 was evaluated on human HCT116, HT29, A549, and H1299 tumor cell lines in vitro, respectively. Whereas, the result showed that these compounds displayed weak cytotoxicity in the human cancer cell lines.

Novel derivatives of plant monomeric phenolics: act as inhibitors of bacterial cell-to-cell communication

The aim of the present study was to synthesize novel active Anti-Quorum sensing derivatives from secondary metabolites viz. Gallic acid, Protocatechuic acid and Vanillic acid present in the plant Bergenia ciliata. Efficacy of all synthesized derivatives have been evaluated on the formation of bacterial biofilm and inhibition of cell-to-cell communication. Anti-Quorum Sensing activity and biofilm formation of all synthesized compounds was measured on biomonitor strain Chrobacterium violaceum, ATCC 12472 using standard paper disk-diffusion assay and quantification of violacein pigment. Among all derivatives, five derivatives 3,4,5-Trihydroxy-benzoic acid methyl ester (9a), 3,4-Dihydroxy-benzoic acid methyl ester (10a), 3,4,5-Tris-(2,4-dichloro-benzyloxy)-benzoic acid methyl ester (12), 3,4,5-Tris-(2,5-dichloro-benzyloxy)-benzoic acid methyl ester (13) and 4-(2,4-Dichloro-benzyloxy)-3-methoxy-benzoic acid methyl ester (15) has shown Anti-Quorum Sensing activity by inhibiting violacein pigment production and biofilm formation without interfering with its growth. The inhibitory effects in violacein pigment production were: positive control (C-30) 72%, (9a), (10a) 47.2%, (12) 27.3%, (13) 40.1% and (15) 22.7% at the concentration of 1 mg/mL and biofilm percent inhibition were found (C-30) 64% (9a) 46.2%, (10a) 40.3%, (12) 18.4%, (13) 35.2%, and (15) 17.3% when compared with the untreated control. Results reveal that synthesized derivatives seem to be good compounds for inhibition and formation of biofilm and AHL-mediated Quorum-sensing mechanism. The present article highlights the importance of derivatives derived from secondary metabolites as potent drug for biofilm formation and inhibition of cell-to-cell communication.

Characterization of volatile compounds in different dried sea cucumber cultivars

Sea cucumber is one of the most well-known and precious seafood in Asian countries. To better understand the sensory properties of dried sea cucumber products, volatile compounds of 8 dried sea cucumber cultivars were analyzed by using solid-phase microextraction (SPME) combined with gas chromatography-mass spectrometry. Forty-two volatile compounds comprising aldehydes (13), alcohols (13), aromatic compounds (9), furans (3), and others (4) were identified. Quantitative results revealed that volatile composition in all tested sea cucumbers were similar, but the variation existed in both the composition and the concentrations of some compounds. The concentration of hexanal, heptanal, 1-heptanol and benzaldehyde varied the most among different sea cucumber cultivars. Besides, 2-methyl-butanal, acetophenone, 2-methyl-furan, benzoic acid methyl ester and dimethyl sulfide were only detected in S. japonicus, a Chinese domestic sea cucumber cultivar, which was the main difference in volatile compounds compared with the other cultivars. There were 17 identified compounds which were considered to be odor-active compounds as their concentrations exceeded their odor detection thresholds in water.

Stabilization of NaBH4 in Methanol Using a Catalytic Amount of NaOMe. Reduction of Esters and Lactones at Room Temperature without Solvent-Induced Loss of Hydride.

Rapid reaction of NaBH4 with MeOH precludes its use as a solvent for large-scale ester reductions. We have now learned that a catalytic amount of NaOMe (5 mol %) stabilizes NaBH4 solutions in methanol at 25 °C and permits the use of these solutions for the reduction of esters to alcohols. The generality of this reduction method was demonstrated using 22 esters including esters of naturally occurring chiral γ-butyrolactone containing dicarboxylic acids. This method permits the chemoselective reductions of esters in the presence of cyano and nitro groups and the reductive cyclization of a pyrrolidinedione ester to a fused five-membered furo[2,3-b]pyrrole and a (-)-crispine A analogue in high optical and chemical yields. Lactones, aliphatic esters, aromatic esters containing electron-withdrawing groups, and heteroaryl esters are reduced more rapidly than aryl esters containing electron-donating groups. The 11B NMR spectrum of the NaOMe-stabilized NaBH4 solutions showed a minor quartet due to monomethoxyborohydride (NaBH3OMe) that persisted up to 18 h at 25 °C. We postulate that NaBH3OMe is probably the active reducing agent. In support of this hypothesis, the activation barrier for hydride transfer from BH3(OMe)- onto benzoic acid methyl ester was calculated as 18.3 kcal/mol.

Effect of alcohol on skin permeation and metabolism of an ester-type prodrug in Yucatan micropig skin

We studied the effect that three alcohols, ethanol (EA), propanol (PA), and isopropanol (IPA), have on the skin permeation of p-hydroxy benzoic acid methyl ester (HBM), a model ester-type prodrug. HBM was applied to Yucatan micropig skin in a saturated phosphate buffered solution with or without 10% alcohol, and HBM and related materials in receptor fluid and skin were determined with HPLC. In the absence of alcohol, p-hydroxy benzoic acid (HBA), a metabolite of HBM, permeated the skin the most. The three alcohols enhanced the penetration of HBM at almost the same extent. The addition of 10% EA or PA to the HBM solution led to trans-esterification into the ethyl ester or propyl ester of HBA, and these esters permeated skin as well as HBA and HBM did. In contrast, the addition of 10% IPA promoted very little trans-esterification. Both hydrolysis and trans-esterification in the skin S9 fraction were inhibited by BNPP, an inhibitor of carboxylesterase (CES). Western blot and native PAGE showed the abundant expression of CES in micropig skin. Both hydrolysis and trans-esterification was simultaneously catalyzed by CES during skin permeation. Our data indicate that the alcohol used in dermal drug preparations should be selected not only for its ability to enhance the solubility and permeation of the drug, but also for the effect on metabolism of the drug in the skin.

An Experimental and Computational Study of 2-(3-Oxo-3H-benzo[f] chromen-1-ylmethoxy)-Benzoic Acid Methyl Ester

The various methods for studying polarities are based on the use of probe molecules, whose molecular spectral profile is significantly affected by the polarity of the medium. The absorption and emission spectra and dipole moments (µ g and µ e) of 2-(3-oxo-3H-benzo[f]chromen-1-ylmethoxy)-benzoic acid methyl ester (2BME) are studied in solvents of different polarities at room temperature. The determination of dipole moments by solvatochromic shift using various relations and the change in dipole moment (Δµ) were determined using Stokes shift with the variation of the solvent polarity parameter (E T N ). The value of µ e greater than µ g indicating that the probe is more polar in the higher state. DFT and TDDFT theoretical analysis of dipole moment in the vacuum and with solvent, solvent accessible surface (SAS) and molecular electrostatic potential (MEP) are also performed.

Selective Targeting of a Novel Vasodilator to the Uterine Vasculature to Treat Impaired Uteroplacental Perfusion in Pregnancy.

Fetal growth restriction (FGR) in pregnancy is commonly caused by impaired uteroplacental blood flow. Vasodilators enhance uteroplacental perfusion and fetal growth in humans and animal models; however, detrimental maternal and fetal side effects have been reported. We hypothesised that targeted uteroplacental delivery of a vasodilator would enhance drug efficacy and reduce the risks associated with drug administration in pregnancy. Phage screening identified novel peptides that selectively accumulated in the uteroplacental vasculature of pregnant mice. Following intravenous injection, the synthetic peptide CNKGLRNK selectively bound to the endothelium of the uterine spiral arteries and placental labyrinth in vivo; CNKGLRNK-decorated liposomes also selectively bound to these regions. The nitric oxide donor 2-[[4-[(nitrooxy)methyl]benzoyl]thio]-benzoic acid methyl ester (SE175) induced significant relaxation of mouse uterine arteries and human placental arteries in vitro; thus, SE175 was encapsulated into these targeted liposomes and administered to healthy pregnant C57BL/6J mice or endothelial nitric oxide synthase knockout (eNOS-/-) mice, which exhibit impaired uteroplacental blood flow and FGR. Liposomes containing SE175 (0.44mg/kg) or PBS were administered on embryonic (E) days 11.5, 13.5, 15.5 and 17.5; fetal and placental weights were recorded at term and compared to mice injected with free PBS or SE175. Targeted uteroplacental delivery of SE175 had no effect on fetal weight in C57BL/6J mice, but significantly increased fetal weight and mean spiral artery diameter, and decreased placental weight, indicative of improved placental efficiency, in eNOS-/- mice; free SE175 had no effect on fetal weight or spiral artery diameter. Targeted, but not free SE175 also significantly reduced placental expression of 4-hydroxynonenal, cyclooxygenase-1 and cyclooxygenase-2, indicating a reduction in placental oxidative stress. These data suggest that exploiting vascular targeting peptides to selectively deliver SE175 to the uteroplacental vasculature may represent a novel treatment for FGR resulting from impaired uteroplacental perfusion.

Tuning of Aggregation Enhanced Emission and Solid State Emission from 1,8-Naphthalimide Derivatives: Nanoaggregates, Spectra, and DFT Calculations.

Four new 1,8-naphthalimide based compounds, 4-(1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-ylmethyl)-benzoic acid (LH), 4-(1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-ylmethyl)-benzoic acid methyl ester (LMe), 4-(1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-ylmethyl)-benzoyl chloride (LCl), and 4-(1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-ylmethyl)-benzoic acid hydrazide (LN) are synthesized and characterized using spectral data and X-ray crystallography. They form nanoaggregates in aqueous-DMF solution and exhibited aggregation enhanced emission. The nanoaggregates are characterized using their scanning electron and atomic force microscopy images. The emission intensity follows the order as LH > LMe > LCl > LN. Their photophysical properties are recorded both in solution and in the solid-state and are correlated with the nature of benzoic acid derivatives owing to the combinatorial effect of π-π stacking and intermolecular and intramolecular interactions. The density functional theory calculations empower the understanding of their molecular and cumulative electronic behaviors. Antiparallel dimeric interactions in the solid-state extend a herringbone arrangement to LH and 2D channel and stair-like arrangement for LCl and LN, respectively.

Differential volatile organic compounds in royal jelly associated with different nectar plants

The aim of this work was to distinguish volatile organic compound (VOC) profiles of royal jelly (RJ) from different nectar plants. Headspace solid-phase microextraction (HS-SPME) was used to extract VOCs from raw RJ harvested from 10 nectar plants in flowering seasons. Qualitative and semi-quantitative analysis of VOCs extracts were performed by gas chromatography-mass spectrometry (GC-MS). Results showed that VOC profiles of RJ from the samples were rich in acid, ester and aldehyde compound classes, however, contents of them were differential, exemplified by the data from acetic acid, benzoic acid methyl ester, hexanoic acid and octanoic acid. As a conclusion, these four VOCs can be used for distinguishing RJ harvested in the seasons of different nectar plants.