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Aims: The present investigation is targeted towards the synthesis of a novel analogue of a natural peptide of marine origin. Background: Marine sponges are enriched with bioactive secondary metabolites, especially circu-lar peptides. Heterocycles are established organic compounds with potential biological value. Tak-ing into consideration the bio-properties of heterocycles and marine sponge-derived natural pep-tides, an effort was made for the synthesis of a heterocyclic analogue of a natural cyclopeptide. Objective : A heterocyclic analogue of a sponge-derived proline-containing cyclic peptide, rolloam-ide A, was synthesized by interaction of Boc-protected L-histidinyl-L-prolyl-L-valine and L-prolyl-L-leucyl-L-prolyl-L-isoleucine methyl ester and compared with synthetic rolloamide A with bioac-tivity against bacteria, fungi, and earthworms. Methods: The synthesis of cycloheptapeptide was accomplished employing the liquid phase method. The larger peptide segment was prepared by interaction of Boc-protected L-prolyl-L-leu-cine with L-prolyl-L-isoleucine methyl ester. Similarly, the tripeptide unit was synthesized from Boc-protected L-histidinyl-L-proline with L-valine ester. The linear heptapeptide segment (7) was cyclized by utilizing pentafluorophenyl (pfp) ester, and the structure was elucidated by elemental and spectral (IR, 1H/13C NMR, MS) analysis. The peptide was also screened for diverse bioactivities such as antibacterial, antifungal, and potential against earthworms and cytotoxicity. Results: The novel cyclooligopeptide was synthesized with 84% yield by making use of car-bodiimides. The synthesized cyclopeptide exhibited significant cytotoxicity against two cell lines. In addition, promising antifungal and antihelmintic properties were observed for newly synthesized heterocyclic peptide derivative (8) against dermatophytes and three earthworm species at 6 μg/mL and 2 mg/mL, respectively. Conclusion: Solution-phase technique employing carbodiimide chemistry was established to be promising for synthesizing the cycloheptapeptide derivative (8), and C5H5N was proved to be a better base for heptapeptide circling when compared to N-methylmorpholine and triethylamine.

This study tests biodegradation resistance of a custom synthesized novel ethylene glycol ethyl methacrylate (EGEMA) with ester bond linkages that are external to the central polymer backbone when polymerized. Ethylene glycol dimethacrylate (EGDMA) with internal ester bond linkages and EGEMA discs were prepared in a polytetrafluoroethylene (PTFE) mold using 40 μl macromer and photo/co-initiator mixture cured for 40 s at 1000 mW/cm(2). The discs were stored in the constant presence of Streptococcus mutans (S. mutans) in Todd Hewitt Yeast + Glucose (THYE+G) media up to 9 weeks ([Formula: see text] for each macromer type) and physical/mechanical properties were assessed. Initial measurements EGEMA versus EGDMA polymer discs showed equivalent degree of conversion (45.69% ± 2.38 vs. 46.79% ± 4.64), diametral tensile stress (DTS; 8.12± 2.92 MPa vs. 6.02 ± 1.48 MPa), and low subsurface optical defects (0.41% ± 0.254% vs. 0.11% ± 0.074%). The initial surface wettability (contact angle) was slightly higher [Formula: see text] for EGEMA (62.02° ± 3.56) than EGDMA (53.86° ± 5.61°). EGDMA showed higher initial Vicker’s hardness than EGEMA (8.03 ± 0.88 HV vs. 5.93 ± 0.69 HV; [Formula: see text]). After 9 weeks of S. mutans exposure, EGEMA ([Formula: see text]) showed higher resistance to biodegradation effects with a superior DTS than EGDMA ([Formula: see text]) [Formula: see text]. Visible and scanning electron microscopy images of EGEMA show less surface cracking and defects than EGDMA. EGDMA had higher loss of material (18.9% vs. 8.5%, [Formula: see text]), relative changes to fracture toughness (92.5% vs. 49.2%, [Formula: see text]) and increased water sorption (6.1% vs. 1.9%, [Formula: see text]) compared to EGEMA discs. The flipped external ester group linkage design is attributed to EGEMA showing higher resistance to bacterial degradation effects than an internal ester group linkage design methacrylate.

Three peppermint oil emulsions using polyglycerol esters of fatty acids-casein (PGFE-CN), polyglycerol esters of fatty acids-sodium caseinate (PGFE-NaCN), and polyglycerol esters of fatty acids-whey protein isolate (PGFE-WPI) as emulsifiers were fabricated, and the droplet size, zeta potential, viscosity, and stability of emulsions were determined. The experimental results showed that the emulsion containing PGFE-CN has relatively smaller droplet size of 231.77 ± 0.49 nm. No significant changes were observed on the average particle size, polydispersity index and zeta potential during 4-week of storage, indicating that the emulsions kept stable against pH, salt ion, freeze-thaw, and storage. Fourier transform infrared spectrometer (FTIR) results showed that the electrostatic interaction occurs between CN and PGFE in the emulsion. The confocal laser scanning microscope (CLSM) was used to observe the microstructure of the emulsion, proving that droplets were evenly distributed throughout the aqueous phase by PGFE-CN emulsifier. The protein-stabilized emulsions can be used as potential carriers for the delivery of the lipophilic nutrients such as peppermint oil. PRACTICAL APPLICATION: PGFE-CN emulsifier can be directly added to the beverage systems containing oil or protein, such as coconut milk, peanut milk, and walnut milk. It can enhance the stability of beverage, prevent the precipitation, stratification, and oil floating, improve the homogeneity of the system and therefore extend the shelf life.

Hypothesis Many ionic surfactants with wide applications in personal-care and house-hold detergency show limited water solubility at lower temperatures (Krafft point). This drawback can be overcome by using mixed solutions, where the ionic surfactant is incorporated in mixed micelles with another surfactant, which is soluble at lower temperatures. Experiments The solubility and electrolytic conductivity for a binary surfactant mixture of anionic methyl ester sulfonates (MES) with nonionic alkyl polyglucoside and alkyl polyoxyethylene ether at 5 °C during long-term storage were measured. Phase diagrams were established; a general theoretical model for their explanation was developed and checked experimentally. Findings The binary and ternary phase diagrams for studied surfactant mixtures include phase domains: mixed micelles; micelles + crystallites; crystallites, and molecular solution. The proposed general methodology, which utilizes the equations of molecular thermodynamics at minimum number of experimental measurements, is convenient for construction of such phase diagrams. The results could increase the range of applicability of MES–surfactants with relatively high Krafft temperature, but with various useful properties such as excellent biodegradability and skin compatibility; stability in hard water; good wetting and cleaning performance.

In this work, free radical photopolymerization (FRP) kinetics for series of different phenylamine oxime ester structures (DMA-P, DEA-P, DMA-M, TP-2P, TP-2M and TP-3M) was investigated. Steric hindrance and branched substituents were prepared to realize the corresponding electronic and photopolymerization effects. The photophysical, electrochemical, thermal properties and radical concentration were investigated by UV-visible spectroscopy, cyclic voltammetry (CV), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and electron paramagnetic resonance (EPR). Furthermore, the structure-reactivity relationships were also studied in detail through photo-DSC experiment. We demonstrate that the introduction of alkyl chains and/or numbers of oxime esters affects significantly the photoreactivity. Under the same weight ratio of formulation and irradiated condition, TP-3M containing three oxime esters in its structure and methyl group in the periphery exhibits the highest double-bond conversion efficiency. TP-3M-based formulation also shows a wide operation window under different contents and light intensities. Importantly, the photoreactivity of the TP-3M-based system was found to be better than the commercial photoinitiator (OXE-01) under LED@405 nm at a low concentration. This work could provide some significance to the design of oxime esters with enhanced photoreactivity.

A modular synthesis of mycobactin T and its N-acetyl analogue is reported in a route that facilitates permutation of the lipid tails. A key feature is the generation of N(α)-Cbz-N(e)-benzyloxy-N(e)-Boc-lysine (A4) with methyl(trifluoromethyl)dioxirane in 59% yield. Selective hydroxamate N-acylation was achieved with acyl fluorides, enabling installation of lipids tails in the final step. O-Benzyl-dehydrocobactin T (B4) was prepared by modifying a known five-step sequence with an overall yield of 49%. 2-Hydroxyphenyl-4-carboxyloxazoline (C3) was prepared from 2-hydroxybenzoic acid and l-serine methyl ester in three steps with an overall yield of 55%. Ester coupling of A4 and B4 with EDCI afforded MbI-1 in 73% yield. Catalytic hydrogenation with Pd/BaSO4 and 50 psi of H2 simultaneously effected alkene reduction and debenzylation to afford MbI-2 in 96% yield. Fragment C3 was converted into acyl fluoride C4, which coupled with MbI-2 to afford MbI-3 in 51% yield. Finally, Boc-removal with HCl/EtOAc and treatment of the resultant hydroxylamine with stearyl fluoride furnished mycobactin T in 65% yield. Overall, the yield is 4% over 14 steps. The gallium mycobactin T-N-acetyl derivative (GaMbT-NAc) structure was determined by 1H NMR. The structure shows an octahedral Ga and two internal hydrogen bonds between peptidic N-Hs and two of the oxygen atoms coordinating Ga.

Radical addition to chiral N-acylhydrazones has generated unusual amino acids tubuphenylalanine (Tup) and tubuvaline (Tuv) that are structural components of the tubulysin family of picomolar antimitotic agents and previously led to a tubulysin tetrapeptide analog with a C-terminal alcohol. To improve efficiency in this synthetic route to tubulysins, and to address difficulties in oxidation of the C-terminal alcohol, here we present two alternative routes to Tuv that (a) improve step economy, (b) provide modified conditions for Mn-mediated radical addition in the presence of aromatic heterocycles, and (c) expose an example of double diastereocontrol in radical addition to a β-benzyloxyhydrazone with broader implications for asymmetric amine synthesis via radical addition. An efficient coupling sequence affords 11-O-benzyltubulysin V benzyl ester.

Despite numerous novel polymeric materials that have been produced by incorporating boronic acid or ester groups into polymers, it remains a challenge to prepare well-defined boronate-containing polymers due to their inherent instability. Herein, we used

Drimane‐type sesquiterpenes exhibit various biological activities and are widely present in eukaryotes. Here, we completely elucidated the biosynthetic pathway of the drimane‐type sesquiterpene esters isolated from Aspergillus calidoustus and we discovered that it involves a drimenol cyclase having the same catalytic function previously only reported in plants. Moreover, since many fungal drimenol derivatives possess a γ‐butyrolactone ring, we clarified the functions of the cluster‐associated cytochrome P450 and FAD‐binding oxidoreductase discovering that these two enzymes are solely responsible for the formation of those structures. Furthermore, swapping of the enoyl reductase domain in the identified polyketide synthase led to the production of metabolites containing various polyketide chains with different levels of saturation. These findings have deepened our understanding of how fungi synthesize drimane‐type sesquiterpenes and the corresponding esters., Reported here is the complete elucidation of the biosynthetic pathway of drimane‐type sesquiterpene esters from Aspergillus calidoustus, including the first identified fungal drimenol cyclase. The cluster‐associated acyltransferase is then employed to transfer different lengths of ACP‐activated polyketides, but also very diverse CoA‐esters.

An atom-economic N-to-C-directed solid-phase peptide synthesis is reported that uses benzyl (Bn) or (benzhydryl-carbamoyl)-methyl (BcM) esters of amino acids as the building blocks, which facilitate efficient hydrazinolysis, convenient conversion to acyl azide, and robust amidation with the next amino acid ester. This method is free of coupling reagents and free of protection on the side-chain OH, CO2H, CONH2, etc., therefore exhibiting a significantly improved atom economy compared to those of BOC- or Fmoc-based C-to-N-directed approaches.

Acyclic asymmetric quaternary stereocenters, which are composed of four carbon-carbon bonds, were finely constructed by utilizing a face-selective alkylation of enolate intermediates derived from an asymmetric Michael addition reaction of a chiral lithium amide with trisubstituted (E)-α,β-unsaturated esters. The present face-selective alkylation was able to employ diverse alkyl halides as an electrophile to afford various Michael adducts having an all-carbon quaternary stereocenter. With regard to the deprotection of the chiral auxiliary, N-iodosuccinimide used in our previous study did not work in the present cases; however, we found that pyridine iodine monochloride in the presence of H2O was effective to remove the bornyl group and the benzyl group on the amino group to provide the β-amino ester derivative.

Research for innovative drugs is crucial to contribute to parasitic infections control and eradication. Inspired by natural antiprotozoal triterpenes, a library of 12 hemisynthetic 3‐O‐arylalkyl esters was derived from ursolic and oleanolic acids through one‐step synthesis. Compounds were tested on Trypanosoma, Leishmania and the WI38 cell line alongside with a set of triterpenic acids. Results showed that the triterpenic C3 esterification keeps the antitrypanosomal activity (IC50≈1.6–5.5 μm) while reducing the cytotoxicity compared to parent acids. Unsaturation of the ester alkyl chain leads to an activity loss interestingly kept when a sterically hindered group replaces the double bond or shields the ester group. An ursane/oleanane C3 hydroxylation was the only important feature for antileishmanial activity. Two candidates, dihydrocinnamoyl and 2‐fluorophenylpropionyl ursolic acids, were tested on an acute mouse model of African trypanosomiasis with significant parasitemia reduction at day 5 post‐infection for the dihydrocinnamoyl derivative. Further evaluation on other alkyl/protective groups should be investigated both in vitro and in vivo., A library of 12 C3 triterpenic esters was readily synthesized and tested for antiparasitic activity and cytotoxicity evaluation. C3 esterification kept the activity while lowering the cytotoxicity. The most potent antitrypanosomal activity, coupled with great selectivity, was shown by 2‐fluoro phenylpropionate, phenylpropionate and α‐methyl phenylpropionate esters of ursolic acids. The phenylpropionate derivative showed significant in vivo parasitemia reduction at day 5 post‐infection.

Hyperbaric oxygen (HBO2) is breathing >1 atmosphere absolute (ATA; 101.3 kPa) O2 and is used in HBO2 therapy and undersea medicine. What limits the use of HBO2 is the risk of developing central nervous system (CNS) oxygen toxicity (CNS-OT). A promising therapy for delaying CNS-OT is ketone metabolic therapy either through diet or exogenous ketone ester (KE) supplement. Previous studies indicate that KE induces ketosis and delays the onset of CNS-OT; however, the effects of exogeneous KE on cognition and performance are understudied. Accordingly, we tested the hypothesis that oral gavage with 7.5 g/kg induces ketosis and increases the latency time to seizure (LSz) without impairing cognition and performance. A single oral dose of 7.5 g/kg KE increases systemic β-hydroxybutyrate (BHB) levels within 0.5 h and remains elevated for 4 h. Male rats were separated into three groups: control (no gavage), water-gavage, or KE-gavage, and were subjected to behavioral testing while breathing 1 ATA (101.3 kPa) of air. Testing included the following: DigiGait (DG), light/dark (LD), open field (OF), and novel object recognition (NOR). There were no adverse effects of KE on gait or motor performance (DG), cognition (NOR), and anxiety (LD, OF). In fact, KE had an anxiolytic effect (OF, LD). The LSz during exposure to 5 ATA (506.6 kPa) O2 (≤90 min) increased 307% in KE-treated rats compared with control rats. In addition, KE prevented seizures in some animals. We conclude that 7.5 g/kg is an optimal dose of KE in the male Sprague-Dawley rat model of CNS-OT.

A continuous flow approach to access α-trifluoromethylthiolated esters and amides using commercially available arylacetic acids and N-(trifluoromethylthio)phthalimide as the electrophilic reagent is described. The experimental protocol involves the in-flow conversion of the carboxylic acid into N-acylpyrazole followed by the α-trifluoromethylthiolation in a PTFE coil reactor and final reaction with primary or secondary amines, or alcohols, to afford in a telescoped process α-substituted SCF3 amides and esters, respectively, in good overall yield and short reaction times.

Fatty acid esters of hydroxy fatty acids (FAHFAs) are a new class of endogenous lipids with promising physiological functions in mammals. We previously introduced a new type of lipids to this family called short-chain fatty acid esters of hydroxy fatty acids (SFAHFAs), branching specific to the C2 carbon of a long-chain fatty acid (≥C20). In this study, we discovered a homologous series of SFAHFAs comprising C16-C26 hydroxy fatty acids esterified with short-chain fatty acids (C2-C5) in mouse colon contents. The detected SFAHFAs were characterized by high-resolution mass spectrometry with MSn analysis. The double-bond position of monounsaturated SFAHFAs was determined by the epoxidation reaction of samples with m-chloroperoxybenzoic acid and their MSn analysis. Further, the measurement of SFAHFA concentration in the colon contents of mice infected with influenza A/Puerto Rico/8/34 (H1N1; PR8) virus revealed a significant increase in their levels compared to native control. A strong correlation was observed between hydroxy fatty acid and SFAHFAs. Detection, characterization, and profiling of these new SFAHFA levels in relation with pandemic H1N1; PR8 influenza virus will contribute to the in-depth study of their function and metabolism.

BACKGROUND Ever since the beginning of agriculture, yields have been threatened by weeds. Chemical weed control is far more effective and economical than other methods. The frequent use of herbicides has led to environmental and human health concerns, resulting in the banning of several herbicides and challenges for the future of important active compounds such as glyphosate. RESULTS The herbicidal activity of sustainable alternatives based on certain esters of fatty acids (FA), the action of which is unrelated to the free acid, on common weeds is assessed and reported. The 13 derivatives of FA showed better physicochemical properties than pelargonic acid-based herbicides. All the reported compounds have phytotoxic activity, the highest efficacy being displayed by the methyl end-capped polyethylene glycol (mPEG) ester of pelargonic acid having 6EO (ethylene oxide). This mPEG ester showed equal or better phytotoxicity than the pelargonic acid benchmark at reduced application rate and spray volume. The active compound is a liquid at ambient temperatures, has no bad smell and is not volatile, in contrast to pelargonic acid. Notably, this active compound can be the final product, can be sprayed without adjuvants and is relatively easy to co-formulate. CONCLUSION A new lead substance is presented that is a sustainable alternative to current contact herbicides. In particular, it has potential application on railways, in precision agriculture and as a harvest aid. Its good performance and technical properties suggest this mPEG ester group may also overcome the volatility-related problems of other organic acids such as auxins. © 2021 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Here, we prepared a series of novel osthole-type ester derivatives modified in the lactone ring of osthole, which is isolated from Cnidium monnieri. The positions of H-3 and H-4 of the representative compound 4z were determined by a 1H-1H COSY spectrum. By opening the lactone ring of osthole, the double bonds at the C-3 and C-4 positions of diol 3 and esters 4a-4z, 4a', and 4b' were still retained as a Z configuration. That is, H-3 and H-4 of compounds 3 and 4a-4z, 4a', and 4b' were all in the cis relationship. The steric configurations of 4k, 4v, and 4z were further undoubtedly determined by single-crystal X-ray diffraction. Against Tetranychus cinnabarinus Boisduval, four aliphatic esters 4c (R = n-C3H7; LC50: 0.31 mg/mL), 4d (R = CH3(CH2)10; LC50: 0.24 mg/mL), 4a' (R = CH3(CH2)9; LC50: 0.28 mg/mL), and 4b' (R = CH3(CH2)12; LC50: 0.32 mg/mL) showed the most promising acaricidal activity, and compounds 4c, 4d, and 4a' also exhibited a potent control efficiency. Especially, compound 4d exhibited greater than fivefold acaricidal activity of the precursor osthole (LC50: 1.22 mg/mL). Against Mythimna separata Walker, compounds 4g, 4l, and 4m displayed 1.6-1.8-fold potent insecticidal activity of osthole. It demonstrated that the lactone ring of osthole is not necessary for the agricultural activities, thiocarbonylation of osthole was not beneficial for the agricultural activities, introduction of R as an aliphatic chain is vital for the acaricidal activity, notably, the length of the aliphatic chain is related to the acaricidal activity, 4d could be further studied as a lead acaricidal agent, and to the aromatic series, R containing the fluorine atom(s) is important for the insecticidal activity.

Lithium cations were observed to accelerate the hydrolysis of esters with hydroxides (KOH, NaOH, LiOH) in a water/tetrahydrofuran (THF) two-phase system. Yields in the hydrolysis of substituted benzoates and aliphatic esters using the various hydroxides were compared, and the effects of the addition of lithium salt were examined. Moreover, it was presumed that a certain amount of LiOH was dissolved in THF by the coordination of THF with lithium cation and hydrolyzed esters even in the THF layer, as in the reaction by a phase-transfer catalyst.

Hexahydroxydiphenoyl (HHDP) and dehydrohexahydroxydiphenoyl (DHHDP) groups are the major acyl components of ellagitannins, which are polyphenols whose biosynthesis have attracted considerable attention; however, the mechanisms of the production of HHDP and DHHDP in the ellagitannin biosynthesis have not been clarified. With the aim of elucidating such a mechanism, this study investigates the CuCl2 -mediated oxidation of simple galloyl derivatives in an aqueous medium. It is shown that the oxidation of methyl gallate affords a DHHDP-type dimer, whose reduction with Na2 S2 O4 yields an HHDP-type dimer. However, the oxidation of the HHDP-type product over CuCl2 does not afford the parent DHHDP ester. The oxidation of 1,4-butanediol digallate under the same conditions produces a DHHDP-type product via the intramolecular coupling of galloyl groups. These results strongly suggest that the DHHDP group is the initial product of the oxidative coupling of two galloyl groups in the ellagitannin biosynthesis, and subsequent reductive metabolism affords HHDP esters.

Among the ribosomally synthesized and post-translationally modified peptide (RiPP) natural products, “graspetides” (formerly known as microviridins) contain macrocyclic esters and amides that are formed by ATP-grasp ligase tailoring enzymes using the side chains of Asp/Glu as acceptors and Thr/Ser/Lys as donors. Graspetides exhibit diverse patterns of macrocylization and connectivities exemplified by microviridins, that have a caged tricyclic core, and thuringin and plesiocin that feature a “hairpin topology” with cross-strand ω-ester bonds. Here, we characterize chryseoviridin, a new type of multicore RiPP encoded by Chryseobacterium gregarium DS19109 (Phylum Bacteroidetes) and solve a 2.44 Å resolution crystal structure of a quaternary complex consisting of the ATP-grasp ligase CdnC bound to ADP, a conserved leader peptide and a peptide substrate. HRMS/MS analyses show that chryseoviridin contains four consecutive five- or six-residue macrocycles ending with a microviridin-like core. The crystal structure captures respective subunits of the CdnC homodimer in the apo or substrate-bound state revealing a large conformational change in the B-domain upon substrate binding. A docked model of ATP places the γ-phosphate group within 2.8 Å of the Asp acceptor residue. The orientation of the bound substrate is consistent with a model in which macrocyclization occurs in the N- to C-terminal direction for core peptides containing multiple Thr/Ser-to-Asp macrocycles. Using systematically varied sequences, we validate this model and identify two- or three-amino acid templating elements that flank the macrolactone and are required for enzyme activity in vitro. This work reveals the structural basis for ω-ester bond formation in RiPP biosynthesis.

New biodegradable polymers are needed for use in drug delivery systems to overcome the high burst release, lack of sustained drug release, and acidic degradation products frequently observed in current formulations. Commercially available poly(lactide-co-glycolide) (PLGA) is often used for particle drug release formulations; however, it is often limited by its large burst release and acidic degradation products. Therefore, a biocompatible and biodegradable tyrosol-derived poly(ester-arylate) library has been used to prepare a microparticle drug delivery system which shows sustained delivery of hydrophobic drugs. Studies were performed using polymers with varying hydrophilicity and thermal properties and compared to PLGA. Various drug solubilizing cosolvents were used to load model drugs curcumin, dexamethasone, nicotinamide, and acyclovir. Hydrophobic drugs curcumin and dexamethasone were successfully loaded up to 50 weight percent (wt %), and a linear correlation between drug wt % loaded and the particle glass transition temperature (Tg) was observed. Both curcumin and dexamethasone were visible on the particle surface at 20 wt % loading and higher. By adjusting the polymer concentration during particle formation, release rates were able to be controlled. Release studies of dexamethasone loaded particles with a lower polymer concentration showed a biphasic release profile and complete release after 47 days. Particles prepared using a higher polymer concentration showed sustained release for up to 77 days. Comparably, PLGA showed a traditional triphasic release profile and complete release after 63 days. This novel tyrosol-derived poly(ester-arylate) library can be used to develop injectable, long-term release formulations capable of providing sustained drug delivery.

Despite increasing awareness of the biological impacts of long-chain fatty acyl-CoA esters (LCACoAs), our knowledge about the subcellular distribution and regulatory functions of these acyl-CoA molecules is limited by a lack of methods for detecting LCACoAs in living cells. Here, we report development of a genetically encoded fluorescent sensor that enables ratiometric quantification of LCACoAs in living cells and subcellular compartments. We demonstrate how this FadR-cpYFP fusion "LACSer sensor" undergoes LCACoA-induced conformational changes reflected in easily detectable fluorescence responses, and show proof-of-concept for real-time monitoring of LCACoAs in human cells. Subsequently, we applied LACSer to investigate how disruption of ACSL enzymes differentially reduces cytosolic and mitochondrial LCACoA levels, and show how genetic disruption of an acyl-CoA binding protein (ACBP) alters mitochondrial accumulation of LCACoAs. Thus, our LACSer sensor achieves spatiotemporally precise detection of dynamic changes in endogenous LCACoA levels in living cells and yields mechanistic insights about metabolism and cellular regulation .

Tea is an important beverage source of dietary polyphenols and well known for containing phenolic structure diversity. A series of phenylpropanoid-substituted catechins, flavonols, flavan-3-hexoside, and proanthocyanidin are present in different herbs with various biological activities, inspiring our exploration of phenylpropanoid-substituted ester type of catechins (PSECs) due to the enrichment of galloylated catechins in tea. In this study, we used a guiding-screening-location-isolation integrated route including creating a hypothesized PSEC dataset, MS/MS data acquiring, construction of molecular networks, and traditional column chromatography and preliminarily identified 14 PSECs by MS/MS spectrum. Two of these PSECs were further purified and elucidated by NMR and CD spectra. Further MS detection in tea products and fresh leaves suggests that the production of the two new compounds was enhanced during tea processing. The synthesis mechanism was proposed to obtain these types of components for further investigation on their roles in human health protection. This study provides an example for the exploration of new functional ingredients from food sources guided by MS/MS data-based networking, and also new insights into the reaction mechanism to form new catechin conjugates among polyphenols in green tea.

Tyrosinase is a key enzyme responsible for enzymatic browning of fruits and vegetables and skin disorders due to overproduction of melanin. Arbutin is an inhibitor of tyrosinase; however, its high polarity and weak transdermal absorption capacity limit its applications. In this paper, a green solvent system was developed to successfully synthesize arbutin esters with improved liposolubilities (Clog P values = 0.27-5.03). Among the obtained esters, arbutin undecenoate (AU) showed the strongest tyrosinase-inhibiting activity (15.6%), which was 9.0 times higher than that of arbutin. An enzyme kinetics study indicated that AU was a competitive inhibitor with reversible inhibition. The esters inhibited tyrosinase by making the secondary structure of tyrosinase looser and less stable; moreover, the interactions between tyrosinase and AU driven by metal interactions and hydrogen bonds also offered a mechanism for inhibition of AU on tyrosinase. In addition, AU (100 μM) reduced the melanin content of B16 mouse melanoma cells to 61.3% of the control group.

The reliable design and prediction of enzyme promiscuity to access transformations not observed in nature remains a long-standing challenge. Herein, we present the first example of an intramolecular stereoselective Stetter reaction catalyzed by benzaldehyde lyase, guided by the rational structure screening of various ThDP-dependent enzymes using molecular dynamics (MD) simulations. After optimization, high productivity (up to 99 %) and stereoselectivity (up to 99:1 e.r.) for this novel enzyme function was achieved.

The amphiphilic humic acid ester ether (HAEE), as a kind of solid-phase extractant with characteristics of easy separation and hydrophilic-hydrophobic amphiphilic property, was prepared and used to extract micro or trace nitrofen, 2,4-dichlorophenol and p-nitrotrophenol (NIPs) from water and soil. Degradation of NIPs and extractant regeneration were carried out by simple photocatalysis. The adsorption equilibrium of the mono- or three mixed NIPs by HAEE in aqueous could be quickly reached within 20 min. The adsorption process was fit to quasi-second-order kinetics model and Friendlich thermodynamics model. The possible adsorption interaction was discussed. Results suggested that the adsorption of NIPs onto HAEE predominated by hydrogen bonding, hydrophobic interaction and π-π interaction. The extraction capacity of mixed NIPs (80 μg/L each component) by HAEE was up to 0.38 mg/g and tended to be multi-layer adsorption, in which p-nitrotrophenol had higher adsorption competitiveness because of lower resistance to HAEE. When HAEE-NIPs were degraded by photo-catalyst Fe

The solubility of oxygen and its transfer rate to the lipid phase play important roles in lipid oxidation, which affects the taste and safety of lipid-containing foods. In this study, we measured the Henry's constants (solubility) of oxygen for fatty acids, fatty acid esters, and triacylglycerols (TAGs; vegetable oils), as well as the mass transfer coefficients of oxygen at the gas- and water-lipid interfaces. The constants and coefficients were estimated by analyzing the change over time in the oxygen partial pressure or concentration in the closed container based on the mass balance equations of oxygen in the gas and liquid phases. The constant for water obtained by the method used in this study was in agreement with the previously reported value to confirm the validity of the method. The constants for lipids depended on the lipid type, and were higher in the order of fatty acid ester, fatty acid, and TAG. That is, the solubility of oxygen decreased in this order. For all lipids, the constant increased as the number of carbon atoms in the fatty acid chain increased. The constants for fatty acids and their esters were linearly correlated with the enthalpies of evaporation of the lipids. The mass transfer coefficients of oxygen at the gas-liquid interface were on the order of 10-5 m/s for water and methyl dodecanoate and of 10-6 m/s for TAG (rapeseed oil). The coefficient at the water-lipid interface was on the order of 10-6 m/s. PRACTICAL APPLICATION: The Henry's constants (solubility) and transfer rate of oxygen to the lipid phase, fatty acids, fatty acid esters, and triacylglycerols (TAG) were measured. The lipids solubilized three to five times more oxygen than water, and mass transfer rate of oxygen at gas- and water-lipid interfaces were almost same. The constants for fatty acids and fatty acid esters were linearly correlated to their enthalpies of evaporation, and this correlation is expected to be useful for estimating the Henry's constants for other fatty acids and their esters.

Enzymatic esterification of resveratrol is crucial for its potential application in lipophilic foods and drugs. However, the poor activity of the free enzyme hinders the reaction. In this work, the highly efficient enzymatic synthesis of resveratrol ester derivatives was achieved by immobilized lipase on hydrophobic modified hollow mesoporous silicon spheres (HMSS-C

Gemcitabine (GMT) is a nucleoside analog used in the treatment of a variety of solid tumors. GMT was chemically modified with a hydrolysable linker, and subsequently incorporated into a poly(anhydride-ester) backbone via melt-polymerization, with the active antimetabolite GMT, thus, becoming the repeat unit that makes up this new material, a biodegradable polymer. Characterization of the structure of polymeric GMT (polyGMT) revealed the incorporation of an average 26 molecules of GMT per polymer chain, which corresponds to a drug loading of 58%w/w. The glass transition temperature of the formed polyGMT was determined to be 123 °C. PolyGMT was engineered into nanoparticles (NPs) using a dialysis-based method, with a resulting geometric diameter of 206 ± 38 nm. The particles are easily dispersible and stable in aqueous-based media, with a hydrodynamic diameter of 229 ± 28 nm. The prepared hydrolysable polyGMT NPs demonstrate ultra-long release profile due to the hydrophobic nature of the linker, and as per characteristic erosion behavior of polymers with anhydride-ester bonds. Accelerated in vitro release studies demonstrate the recovery of free GMT upon hydrolysis, with biological activity as assessed by cytotoxicity assays performed in adenocarcinoma human alveolar basal epithelial (A549) and highly metastatic murine osteosarcoma (K7M2) cells lines. The characteristics of polyGMT, including its thermal properties and built in hydrolysable structure, are thus conducive for use in the preparation of drug delivery systems. Engineered structures prepared with polyGMT can maintain their morphology at ambient and physiologically relevant conditions, and free GMT is recovered as the anhydride and ester bonds are hydrolyzed. This work is innovative as for the first time we demonstrate the ability to polymerize GMT in a hydrolysable polymer structure, and engineer NPs of this polymeric chemotherapy. The synthetic strategy allows for tuning of the polymer hydrophobicity and thus potentialize its behavior, including degradation profile, by varying the linker chemistry. Such controlled release hydrolysable polymers with very high drug loading and controlled erosion profiles are relevant as they may offer new opportunities in drug delivery applications for the treatment of malignant neoplasms.

An expedient synthesis of β-silyl α-amino acids is reported via the application of visible-light-mediated hydrosilylation. The reaction utilizes readily accessible and structurally diverse hydrosilanes to provide radicals for conjugate addition to dehydroalanine ester and analogues. Notably, the use of chiral methyleneoxazolidinone as the substrate and chiral inducer enabled the highly stereoselective synthesis. Furthermore, the reaction could also be performed in a continuous flow fashion and scaled up to the gram scale.

In this research, we studied the antioxidative properties and chemical changes of quercetin in fish oil during accelerated storage at 60 °C for 5 days. Gas chromatography (GC) analysis showed that quercetin inhibited aldehyde formation and unsaturated fatty acid oxidation in fish oil significantly; however, the inhibitory effects decreased gradually with prolonged heating time. Moreover, quercetin was consumed with increasing heating time. Some new phenolic derivatives were discovered in the fish oil with quercetin, with their structures fully elucidated by LC-MS/MS and comparison with newly synthesized ones (characterized by MS and NMR spectroscopy). Based on their chemical structures, we proposed that quercetin reacted with EPA and DHA to form the corresponding quercetin fatty acid esters in fish oil. In addition, the newly formed quercetin-3-O-eicosapentaenoate and quercetin-3-O-docosahexaenoate showed weaker DPPH and ABTS radical cation scavenging activity but much improved lipophilicity, higher cell membrane affinity, and hence enhanced cellular antioxidant activity compared with the parent quercetin. Overall, quercetin could be used as a safe dietary polyphenol to inhibit lipid oxidation. The newly formed quercetin-polyunsaturated fatty acid esters may render improved bioactivity to humans, which needs further investigation.

A method for amide-directed Ni-catalyzed diastereoselective arylboration of cyclopentenes is disclosed. The reaction allows for the synthesis of sterically congested cyclopentane scaffolds that contain an easily derivatized boronic ester and amide functional handles. The nature of the amide directing group and its influence on the reaction outcome are investigated and ultimately reflect a predictably selective reaction based on the solvent and base counterion.

The fatty acid composition of bacterial isolates remains stable under standardized culture conditions, which makes it a useful taxonomic marker. The present study aims to characterize the diversity and quantity of fatty acid methyl esters (FAME) profiles of cultivable bacterial isolates collected along the southwest coast of India. Based on the similarity indices (range > 0.3–0.7) of the FAME profiles, the isolates were aggregated into 10 families, 11 genera and 19 species of cultured isolates. The following classes of bacteria were found: Bacilli, Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria and Actinobacteria, which also included a few pathogens such as Pseudomonas, Staphylococcus and Bacillus sp. The hydroxyl FAMEs 2-hydroxydodecanoic acid (C12:0 2OH), 2-hydroxypentadecanoic acid (C15:0 2OH),3-hydroxy 14-methylpentadecanoic acid (C16:0iso 3OH), 3 hydroxy hexadecenoic acid (C16:0 3OH) and 3-hydroxy 15-methylhexadecanoic acid (C17:0iso 3OH), as well as the unsaturated FAMEs (11Z)-11-hexadecenoic acid (C16:1 ɷ5c), were exclusively associated with the isolates from Mangalore samples. Similarly, FAMEs 2-hydroxydecanoic acid (C10:0 2OH), 9-methyldecanoic acid (C11:0iso), undecanoic acid (C11:0), tridecanoic acid (C13:0), 10-methylhexadecanoic acid (C16:0 10-CH3) and (7Z)-7-hexadecenoic acid (C16:1 ɷ9c) occurred only in the isolates from Trivandrum samples. However, the isolates from Goa did not possess a signature FAME profile. The reproducibility of the GC-MIDI bacterial identification system was evaluated using 16S rRNA gene sequencing techniques for selected isolates.

We report a glucose-based crown ether capable of chiral recognition of a wide range of amino-acid methyl esters in aqueous environments. The enantioselectivities towards amino-acids with extended hydrophobic side chains displayed by the glucose-derived macrocycle are among the highest observed for small molecule synthetic receptors to date.

Methyl groups were introduced on the acridine moiety in chemiluminescent acridinium esters that have electron-withdrawing groups (trifluoromethyl, cyano, nitro, ethoxycarbonyl) at the 4-position on the phenyl ester. The introduction of methyl groups at the 2-, 2,7-, and 2,3,6,7-positions on the acridine moiety shifted the optimal pH that gave relatively strong chemiluminescence intensity from neutral conditions to alkaline conditions. 4-(Ethoxycarbonyl)phenyl 2,3,6,7,10-pentamethyl-10λ4-acridine-9-carboxylate, trifluoromethanesulfonate salt showed long-lasting chemiluminescence under alkaline conditions. Acridinium esters to determine hydrogen peroxide concentration at pH 7-10 were newly developed.

Supplemental Digital Content is available in the text., Background: Accumulating evidence suggests that the failing heart reprograms fuel metabolism toward increased utilization of ketone bodies and that increasing cardiac ketone delivery ameliorates cardiac dysfunction. As an initial step toward development of ketone therapies, we investigated the effect of chronic oral ketone ester (KE) supplementation as a prevention or treatment strategy in rodent heart failure models. Methods: Two independent rodent heart failure models were used for the studies: transverse aortic constriction/myocardial infarction (MI) in mice and post-MI remodeling in rats. Seventy-five mice underwent a prevention treatment strategy with a KE comprised of hexanoyl-hexyl-3-hydroxybutyrate KE (KE-1) diet, and 77 rats were treated in either a prevention or treatment regimen using a commercially available β-hydroxybutyrate-(R)-1,3-butanediol monoester (DeltaG; KE-2) diet. Results: The KE-1 diet in mice elevated β-hydroxybutyrate levels during nocturnal feeding, whereas the KE-2 diet in rats induced ketonemia throughout a 24-hour period. The KE-1 diet preventive strategy attenuated development of left ventricular dysfunction and remodeling post-transverse aortic constriction/MI (left ventricular ejection fraction±SD, 36±8 in vehicle versus 45±11 in KE-1; P=0.016). The KE-2 diet therapeutic approach also attenuated left ventricular dysfunction and remodeling post-MI (left ventricular ejection fraction, 41±11 in MI-vehicle versus 61±7 in MI-KE-2; P

This review highlights recent developments in the field of biodegradable polymeric materials intended to replace non-degradable conventional plastics, focusing on studies from the last ten years involving the stereoselective ring-opening polymerization of cyclic esters. This encompasses exciting advances in both catalyst design and monomer scope. Notably, the last decade has seen the emergence of metal-free stereocontrolled ROP for instance, as well as the synthesis and stereocontrolled polymerization of new types of chiral monomers. This study will emphasize recent stereoselective polymerization catalysts and chiral monomers and will focus on stereocontrol quantification, the mechanisms of stereocontrol and their differentiation if reported and studied for a specific catalyst system.

A series of halo-substituted mixed ester/amide-based analogues 4a-l have been prepared as jack bean urease inhibitor, which showed good to excellent inhibition of enzyme activity. The role of halo-substituted benzoyl moieties and alkyl substituted anilines in urease inhibitory kinetics was also investigated. The alkyl-substituted anilines 1a–b reacted with chloroacetyl chloride to afford intermediates 2a-b, which were then reacted with different halo-substituted benzoic acids 3a–f to prepare the title compounds 4a-l. The chemical structures of final products 4a-l were ascertained by FTIR, 1H NMR, 13C NMR, and mass spectra. The compound 4b showed remarkable activity with IC50 1.6 ± 0.2 nM, better than the standard thiourea having IC50 472.1 ± 135.1 nM. The 2-chloro-substituted phenyl ring on one side of compound 4b and 4-isopropyl-substituted benzene on the other side play an essential role in inhibition of urease activity. Lineweaver–Burk plots (kinetics study) indicated about 4b derivative as a mixed type of inhibitor. The virtual screening performed against urease enzyme (PDBID 4H9M) showed that compounds 4b and 4e have binding energies of −7.8 and −7.9 Kcal/mol, respectively. Based upon our results, it was found that derivative 4b is a highly potent urease inhibitor, better than the standard thiourea.

A fosmid metagenomic library containing 9.7 × 104 clones was constructed. A novel esterase, XtjR8, was isolated through functional screening. XtjR8 shared the maximum amino acid identity (44%) with acetyl-hydrolase from Streptomyces hygroscopicus, and was classified into family IV esterase. XtjR8 exhibited the highest hydrolytic activity for p-nitrophenyl acetate at 40 °C and pH 8.0, and presented more than 40% activity from 20 °C to 80 °C. More importantly, XtjR8 displayed the ability to hydrolyze both phthalate monoesters and diesters, this feature is extremely rare among previously reported esterases. Site-directed mutagenesis experiments revealed that the catalytic triad residues were Ser152, Glu246, and His276. Among them, Ser152 formed a hydrogen bond with dibutyl phthalate (DBP) by molecular docking, Gly84, Gly85, and Leu248 of conserved motifs formed hydrophobic interactions with DBP, respectively, which were important for the catalytic activity. Considering its wide range of temperature and hydrolytic potential toward phthalate esters, XtjR8 will be served as an interesting candidate for biodegradation and industrial applications.

To determine if meconium fatty acid ethyl esters (FAEE) in rat pups is a good biomarker of prenatal exposure and effect to alcohol, three groups of pregnant rats were studied: one control (pair fed) and two treatment groups given 25% alcohol at 2.2 or 5.5 g−1 kg−1 d−1. The pups were delivered on day 20 and, for each dam, were separated into a male and female group. The body, brain, intestines, and placenta of the pups were obtained, weighed, and stored at −20°C. The pups’ intestines (as surrogate of meconium) from each group were pooled, and meconium was analyzed by gas chromatography/mass spectroscopy for FAEE. The meconium showed the following FAEE: ethyl palmitate, ethyl stearate, and ethyl linolenate and were only found in the alcohol-treated group and with high specificity but low sensitivity. Mean body weight of the pups was lower in the treatment groups compared to the control groups. Ethyl palmitate concentration correlated negatively to the pups’ mean body and brain weights. Therefore, ethyl palmitate, stearate, and linolenate, in meconium of rat pups prenatally exposed to alcohol, are useful biomarkers of prenatal alcohol exposure, with ethyl palmitate a good biomarker of adverse effect on the pups’ body and brain weight.

Background:: Phytochemical studies on the ethanolic extract of aerial parts of Alstonia scholaris lead to the isolation of two new triterpenoid of the lanostanetype, lanosta 5ene,24-ethyl-3-O-β-D-glucopyranoside (1), lanosta,5ene,24-ethyl-3-O-β-D-glucopyranosideester (2) and new ursane type triterpenoidmethylester, 12-ursene-2,3,18,19-tetrol,28 acetate (nighascholarene) (3), together with seven known triterpenes, betuline, triterpene of the lupane type, alstoprenyol (4), 3β-hydroxy-28-β-acetoxy-5-olea triterpene (5),α-amyrin acetate (6), α-amyrin (7), lupeol acetate (8), 3β-hydroxy-24-nor-urs-4,12,28-triene triterpene (9) and ursolic acid (l0). Methodology:: The triterpenoid structures of these colorless compounds were deduced from the 1H and 13C-NMR data, and in particular from the application of two-dimensional 1H, 13C correlation experiments as well as by comparison with reported literature data. Results and Conclusion: This study deals with isolation and structural elucidation of natural new triterpenoidesters and glycosides with anti-inflammatory activity.

Current dental sealants with methacrylate based chemistry are prone to hydrolytic degradation. A conventional ethylene glycol dimethacrylate (EGDMA) was compared to a novel methacrylate monomer with a flipped external ester group (ethylene glycol ethyl methacrylate - EGEMA) that was designed to resist polymer degradation effects. Fourier transform infrared spectroscopy and water contact angle confirmed a comparable degree of initial conversion and surface wettability for EGDMA and EGEMA. EGDMA disks initially performed better compared to EGEMA as suggested by higher surface hardness and 1.5 times higher diametral tensile strength (DTS). After 15 weeks of hydrolytic and accelerated aging, EGDMA and EGEMA DTS was reduced by 88% and 44% respectively. This accelerated aging model resulted in 3.3 times higher water sorption for EDGMA than EGEMA disks. EGDMA had an increase in grain boundary defects and visible erosion sites with accelerated aging, while for EGEMA the changes were not significant.

A series of new solid esters was synthesized by using greener chemistry strategy involving simple reaction of an alcohol with sulfonamide ligand. Characterization study of these methyl (1), ethyl (2) isopropyl (3) and n-butyl (4) ester of 4-((4-chlo-rophenylsulfonamido)methyl)cyclohexanecarboxylic acid was done by using FTIR, NMR mass spectrometry and X-ray crystallography. The compounds were optimized with Gaussian software according to basis set B3LYP/6-31G(d,p) and their different parameters related to structure were calculated. Furthermore, all compounds of the series were screened for their in vitro biological applications involving anti-bacterial (Chromohalobactor salixgens, Halomonas halofila, Escherichia coli, Staphylococcus aureus, Bacillus subtilis, and Shiegella sonnei), anti-fungal (Aspergillus niger), anti-oxidant (DPPH scavenging activity) and enzyme inhibition (acetylcholine esterase and butyrylcholine esterase) study. Sulfonamide based esters were also docked against selected enzymes (AChE and BChE) using MOE software for their mode of binding. Results obtained from these biological evaluations showed that such compounds have potential against targeted activity.

Polysorbate 20 (PS20) is a commonly used surfactant in biopharmaceutical formulations. It is a heterogeneous surfactant containing a distribution of fatty acid esters, which are subject to hydrolytic degradation, generating free fatty acids (FFAs). The FFAs can form visible or subvisible particles in drug product on stability. A previous FFA solubility model, developed by our group, predicts solubility limits for the three most prevalent FFA degradation products of PS20: lauric, myristic, and palmitic acid. The model takes into account two formulation parameters, pH and PS20 concentration, and their effect on FFA solubility. This work identifies a third parameter that has an impact on FFA solubility: PS20 ester distribution. When PS20 is hydrolytically degraded, the ester distribution of the remaining surfactant changes on stability. Ester distribution is known to influence the critical micelle concentration (CMC) of PS20 such that the monoesters have a much higher CMC compared to the higher-order esters (HOE). We hypothesize that as PS20 degrades, the CMC changes, affecting the proportion of PS20 that is present in micelles and capable of sequestering and solubilizing FFAs in these micelles. Here, PS20 was separated into monoester, HOE, and polyol fractions. The monoester and HOE fractions were mixed together to generate the mock degradation profiles of hydrolytically degraded PS20. FFA solubility was measured as a function of the concentration of these mock-degraded (MD) PS20s. The results indicate that ester distribution does have an impact on FFA solubility, especially at higher MD PS20 concentrations. HOEs solubilize up to 30 μg/mL more lauric acid than an equivalent amount of monoesters at a MD PS20 level of 0.06% w/v. With the addition of % HOE peak area fraction as a third parameter representing the ester distribution of PS20, the refined FFA solubility model more accurately predicts FFA solubility in protein formulations at 5 °C. The refined model suggests that drug products containing trace levels of host cell proteins (HCPs) that preferentially degrade HOEs of PS20 are at a higher risk of particle formation.

In this study, a high methyl ester pectin polysaccharide, AER-A3 (Mw, 1.12 × 105 g/mol; O-methyl ester groups (wt%), 3.81%), was isolated and purified from the root bark of Aralia elata by ion exchange and gel-filtration chromatography. Its planar structure was investigated in combination with UPLC-ESI+-MS, FT-IR, HILIC-UPLC-ESI−-HCD-MS/MS, GC–MS and NMR techniques. The main chain of AER-A3 was unambiguously determined to be smooth region and hairy region with a chain length ratio of 1:1, characterized by occurrence of (1 → 2)-α-Rhap, (1 → 2,3)-α-Rhap, (1 → 2,4)-α-Rhap, (1 → 2,3,4)-α-Rhap, and (1 → 4)-α-GalpA, whereas the branched chain included T-α-Rhap, T-α-Araf, (1 → 5)-α-Araf, (1 → 3,5)-α-Araf, T-β-Galp, (1 → 3)-β-Galp, (1 → 3,4,6)-β-Galp, (1 → 4)-Glcp, (1 → 3)-Glcp, and (1 → 3)-Manp. Meanwhile, SEC-MALLS-RID, CD and Congo red assays showed that AER-A3 had no helical conformations but existed as a globular shape with branching. In addition, AER-A3 had good scavenging activities against DPPH, hydroxyl, and superoxide radicals. Anti-tumor assay investigated the effects of AER-A3 on human A549 and HepG2 cancer cell lines in vitro. These results provided a scientific basis for the use of the polysaccharides in A. elata root barks in pharmaceuticals.

Targeted covalent inhibitors designed to bind covalently to a specific molecular target have recently been a focus of drug development. Among these inhibitors, thiol compounds bind covalently to endogenous thiols in the body through a process involving disulfide bonds. We investigated the predictability of changes in the exposure to captopril, tiopronin, the active form of dalcetrapib and the active metabolite of prasugrel, R-138727, all of which have a sulfhydryl group, in moderate and severe chronic kidney disease (CKD) patients using a constructed PBPK model. The changes in the exposure to captopril, tiopronin and the active form of dalcetrapib under CKD conditions were well predicted. However, the change in exposure to R-138727, which is a secondary metabolite of prasugrel, was overpredicted. Although these thiol compounds covalently bind to endogenous thiols, our study concluded that changes in exposure to these compounds under CKD conditions can probably be predicted, except for compounds with a complicated mechanism whereby the thiol metabolite is generated.

The notable physical and chemical properties of sucrose fatty acid esters have prompted their use in the chemical industry, especially as surfactants, since 1939. Recently, their now well-recognized value as nutraceuticals and as additives in cosmetics has significantly increased demand for ready access to them. As such a review of current methods for the preparation of sucrose fatty acid esters by both chemical and enzymatic means is warranted and is presented here together with an account of the historical development of these compounds as surfactants (emulsifiers). The somewhat belated recognition of the antimicrobial, anticancer and insecticidal activities of sucrose esters is also discussed along with a commentary on their structure-property profiles.

Oleogels were prepared by emulsion template method through 3.0% tea polyphenol ester (Tp-ester) particles with four fatty acid chain length (Tp-laurate [C12], Tp-myristate [C14], Tp-palmitate [C16], and Tp-stearate [C18]) and 2.5% citrus pectin, and then were used in cookie production as fat replacer. Effects of the fatty acid chain length on the hydrophilicity/hydrophobicity of Tp-ester, on the appearance, microstructure, and firmness of dried products, on rheological features of oleogels, on the dynamic viscoelasticity and textural characteristics of cookies dough, and on cookies qualities were revealed. With the increase in the fatty acid chain length, the θo and θw values of four Tp-esters increased, the firmness of dried products with smaller oil droplets got larger, and the gel intensity of oleogels increased, but the quality scores, spread ratio, and break strength of the cookies did not change significantly. With the increase in the replacement levels of butter with oleogels, the harder cookie dough with weaker gel strength and the softer cookies with lower hedonic scores and crispness were found. At 25% and 50% replacement levels, cookies prepared with oleogels using Tp-palmitate or Tp-stearate particles exhibited similar hedonic scores, break strength, spread ratio, and storage stabilities to that of butter cookies. PRACTICAL APPLICATION: Cookies are relished by all age groups due to their taste and crispness, but include high content of saturated fatty acids that are harmful to people's health. The result of this study will help the industry to better design cookies through oleogels with tea polyphenols ester and pectin, and will provide healthy cookies with little or no butter for consumers.

Lipase hydrolyses the ester bonds in triglyceride. It is an important enzyme in medicine and industry. Some pathogen bacteria use this exoenzyme to disrupt the extracellular matrix of host organisms. Pseudomonas uses various extracellular enzymes such as lipase to invade its host. In this report, for the first time, bromhexine was introduced as an inhibitor of lipase. Bromhexine is a mucolytic drug which is used in the treatment of respiratory tract disorders. The results showed that bromhexine inhibited the enzyme by competitive inhibition. IC50 and Ki values of the drug were 0.049 mM and 0.02 mM, respectively. Arrhenius plot showed that the drug reduced the activation energy. The enzyme was purified and SDS-PAGE showed that its molecular weight is 13 kDa. Fluorescence measurement revealed that binding of the drug to lipase could make structural changes in the enzyme. Inhibition of lipase by bromhexine could be applicable in medicine.

OBJECTIVE The aim of this study was to examine the effects of a ketone ester (KE)-supplemented diet on energy expenditure (EE) and adiposity in mice housed at 23 °C versus thermoneutrality (30 °C), in which sympathetic nervous system activity is diminished. METHODS Thirty-two 10-week-old male C57BL/6J mice were assigned to 1 of 4 groups (n = 8 per group): 30% KE diet + 23 °C (KE23), control (CON) diet + 23 °C (CON23), 30% KE diet + 30 °C (KE30), or CON diet + 30 °C (CON30). CON mice were pair-fed to the average intake of mice consuming the KE diet (ad libitum) for 8 weeks. Body composition and components of energy balance were measured at completion of the study. RESULTS CON23 (mean ± SD, 26.0 ± 1.6 g) and CON30 (29.7 ± 1.4 g) mice weighed more than KE groups (P