Ethyl Ester Group Research Articles

Hyaluronic acid conjugates of glycine peptides and L-tryptophan

This work reports about the conjugation of glycine C-terminal ethyl and methyl ester peptides and L-tryptophan methyl ester with sodium hyaluronate in aqueous solutions using the peptide coupling agent DMTMM (or short DMT, 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methyl-morpholinium chloride). Detailed infrared (IR) absorbance and 1H and 13C (2D) NMR studies (heteronuclear multi-bond correlation spectroscopy, HMBC) confirmed covalent and regioselective amide bonds with the D-glucuronate, but also proves the presence of DMT traces in all conjugates. The ethyl ester`s methyl protons on the peptides` C-terminal could be used to quantify the degree of substitution of the peptide on the hyaluronate scaffold by NMR. The ester group also proved stable during conjugation and work-up, and could in some cases be selectively cleaved in water whilst leaving the amide bond intact as shown by potentiometric charge titration, NMR and IR. The conjugates did not influence the capability of human umbilical vein endothelial cells (HUVECs) to reduce MTS (5-[3-(carboxymethoxy)phenyl]-3-(4,5-dimethyl-2-thiazolyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt) to a formazan dye, which points towards a low cytotoxicity for the obtained products. The conjugation method and products could be tested for tissue engineering gels or drug delivery purposes with alternative, biologically active peptides.

Cytotoxic Effect of YH239-EE and Its Enantiomer on MCF7 Cell Line.

This study aimed to discover the cytotoxic effect of YH239-EE and YH239 alone and their enantiomer potency in cytotoxic effect on the MCF7 cell line. We used the cytotoxic study on MDM2 cell lines by detecting the percentage of apoptosis and necrosis by annexin v methods. This result shows that YH239-EE causes more apoptosis and necrosis 40% in comparison to YH239 without ethyl ester, about 4.92 %, and The (+) enantiomer of YH239-EE demonstrated a markedly higher induction of apoptosis and necrosis (84.48%) in MCF7 cells compared to the (-) enantiomer (48.71%). The ethyl ester group in YH239-EE might play a crucial role in enhancing the compound's ability to induce cell death, and The high efficacy of the (+) enantiomer of YH239-EE in inducing cell death in MCF7 cells suggests it may be a more promising therapeutic candidate for breast cancer treatment, specifically for subtypes represented by MCF7 cells.

Comparison of Efficacy between Pemafibrate and Omega-3-Acid Ethyl Ester in the Liver: the PORTRAIT Study.

No pharmacotherapeutic treatment has been established for metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). This trial compared the effects of pemafibrate and omega-3-acid ethyl ester on hepatic function in patients with hypertriglyceridemia complicated by MASLD. Patients with hypertriglyceridemia complicated by MASLD were enrolled, randomly assigned to the pemafibrate or omega-3-acid ethyl ester group, and followed for 24 weeks. The primary endpoint was the change in alanine aminotransferase (ALT) from baseline to week 24. The secondary endpoints included other hepatic enzymes, lipid profiles, and hepatic fibrosis biomarkers. A total of 80 patients were enrolled and randomized. The adjusted mean change in ALT from baseline to week 24 was significantly lower in the pemafibrate group (-19.7±5.9 U/L) than in the omega-3-acid ethyl ester group (6.8±5.5 U/L) (intergroup difference, -26.5 U/L; 95% confidence interval, -42.3 to -10.7 U/L; p=0.001). Pemafibrate significantly improved the levels of other hepatic enzymes (aspartate aminotransferase and gamma-glutamyl transpeptidase), lipid profiles (triglycerides, total cholesterol, high-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol), and hepatic fibrosis biomarkers (Mac-2 binding protein glycan isomer and Fibrosis-4 index). No cases of discontinuation due to adverse drug reactions were identified in either group, and there were no safety concerns. Pemafibrate is recommended over omega-3-acid ethyl ester for lipid management and MASLD treatment in patients with hypertriglyceridemia complicated by MASLD. The study results may contribute to the development of future treatment strategies for patients with MASLD/MASH.

Development of Self-Assembling bis-1,4-Dihydropyridines: Detailed Studies of Bromination of Four Methyl Groups and Bromine Nucleophilic Substitution.

One of the most important steps in the synthesis of 1,4-dihydropyridine (1,4-DHP) amphiphiles is the bromination of methyl groups in positions 2 and 6 of the entire ring. However, up to now, only N-bromosuccinimide was mainly used for bromination 1,4-DHPs. In this work, the synthesis of bis-1,4-DHP derivatives with ethyl and dodecyl ester groups attached to 1,4-DHP ring at positions 3 and 5 was performed by Hantzsch synthesis. The experimental studies were carried out to find out the best conditions and the agent for the tetra bromination of bis-1,4-DHP methyl groups at positions 2 and 6. Four different brominating agents were screened. The use of pyridinium bromide-perbromide in ethyl acetate was found to be optimal for the bromination of methyl groups. The bromination reaction was followed by the synthesis of cationic pyridine moiety containing amphiphilic bis-1,4-DHP derivatives. By nucleophilic substitution of bromine with various substituted pyridines, 12 new amphiphilic bis-1,4-DHP derivatives were obtained. Evaluation of self-assembling properties of tetracationic bis-1,4-dihydropyridine derivatives by dynamic light scattering (DLS) measurements was also performed.

Effects of subphase pH and temperature on the interfacial behavior of double hydrophilic diblock copolymer PDEGMA‐b‐PDIPAEMA

AbstractThe aggregation behavior of two pH‐ and temperature‐responsive diblock copolymers of poly[di‐(ethylene glycol) methyl ether methacrylate]‐block‐poly[2‐(diisopropylamino) ethyl methacrylate] (PDEGMA‐b‐PDIPAEMA) at the air/water interface and the structures of their Langmuir–Blodgett (LB) films were studied by the Langmuir monolayer technique and atomic force microscopy, respectively. At the air/water interface, PDEGMA‐b‐PDIPAEMA tends to form the core‐shell‐corona micellar structure composed of a PDIPAEMA main chain core, an amino ethyl ester shell, and a PDEGMA corona. Under acidic, neutral, and alkaline conditions, PDIPAEMA blocks are completely protonated, partially protonated, and completely non‐protonated, respectively, and the protonated amino ethyl ester groups are immersed in water before monolayer compression, whereas PDEGMA coronas are adsorbed at the interface. At pH 3, 7, and 10, the limiting areas (A0) for PDEGMA42%‐PDIPAEMA58% (weight percents) and PDEGMA55%‐PDIPAEMA45% are 8.2/10.2/14.0 and 6.7/8.3/8.4 nm2, respectively. The A0 values of the former copolymer are larger than those of the latter. This is because the shells in the former copolymer are denser due to the higher polymerization degree of PDIPAEMA blocks, providing greater steric hindrance for PDEGMA coronas and making the latter more extended at the interface. In contrast to other copolymer systems, the effect of temperature on the isotherms of PDEGMA‐b‐PDIPAEMA is less obvious.

Design, Synthesis, and Antisickling Investigation of a Thiazolidine Prodrug of TD-7 That Prolongs the Duration of Action of Antisickling Aromatic Aldehyde.

The synthetic allosteric effector of hemoglobin, TD-7 has been investigated as a potential therapeutic agent for the treatment of sickle cell disease. The pharmacologic activity of TD-7 is due to formation of a Schiff-base interaction between its aldehyde group and the two N-terminal αVal1 amines of hemoglobin, effectively inhibiting sickling of red blood cells. However, TD-7 faces a challenge in terms of poor oral bioavailability due to rapid in-vivo oxidative metabolism of its aldehyde functional group. To address this shortcoming, researches have explored the use of a L-cysteine ethyl ester group to cap the aldehyde group to form a thiazolidine aromatic aldehyde prodrug complex, resulting in the improvement of the metabolic stability of this class of compounds. This report details the synthesis of a thiazolidine prodrug of TD-7, referred to as Pro-7, along with a comprehensive investigation of Pro-7 functional and biological properties. In an in-vitro Hb modification and Hb oxygen affinity studies using normal whole blood, as well as erythrocyte sickling inhibition using sickle whole blood, Pro-7 exhibited a gradual onset but progressive increase in all activities. Additionally, in-vivo pharmacokinetic studies conducted with Sprague Dawley rats demonstrated that Pro-7 can undergo hydrolysis to release TD-7. However, the blood concentration of TD-7 did not reach the desired therapeutic level. These findings suggest that the incorporation of the L-cysteine ethyl ester group to TD-7 represents a promising strategy to enhance the metabolic stability of aromatic aldehydes that could lead to the development of a more effective drug for the treatment of sickle cell disease.

Thiophene-conjugated benzothiazole derivatives as versatile skeletons for staining subcellular organelles in living cells

A series of hydroxy thiophene-conjugated benzothiazole derivatives (HTBs) was prepared to investigate their fluorescence emission behaviors and capability to selectively stain subcellular organelles for fluorescence imaging. The HTB derivatives exhibited excited-state intramolecular proton transfer (ESIPT) and intramolecular charge transfer (ICT) behaviors, according to their molecular structure. Subtle changes in the molecular structure of the HTB influenced its response to changes in the surrounding environment, such as the solvent polarity and/or pH. In vitro cellular imaging experiments revealed that HTBA (5-(benzo[d]thiazol-2-yl)-[2,2′-bithiophen]-4-ol) could selectively stain mitochondria. In contrast, HTBB-CO2Et (ethyl 5'-(benzo[d]thiazol-2-yl)-3′-hydroxy-[2,2′-bithiophene]-5-carboxylate), which contains a regioisomeric hydroxy thiophene unit with an electron-withdrawing ethyl ester group, showed the capability to stain lipid droplets (LDs) in living cells. When the hydroxyl group in HTBB-CO2Et was protected with a benzyl group, effective staining of LDs in live cells was achieved. Thus, we successfully obtained an effective fluorescent probe. Collectively, the results indicated that small structural changes resulted in substantial changes in the intracellular localization and in vitro imaging ability of the prepared compounds.

Synthesis, in silico, and evaluation of AChE inhibitory activity of N-phthaloylphenylglycine derivatives as potential anti-Alzheimer’s agents

Mental illnesses are one of the most relevant health problems today, among which Alzheimer’s disease (AD) stands out. This is a severe disease that entails different alterations such as chronic cognitive impairment. Commercial therapy drugs have not had the expected success due to their notable and rapid pharmacological efficacy reduction, therefore, we aimed to find new compounds capable of stopping the progression of this disease by cholinesterase inhibition. We synthesized and evaluated nine new racemic compounds (two precursors and their corresponding pyrrolo[2,1-a]isoindol-5-ones with different substituents) derived from phenylglycine as potential acetylcholinesterase inhibitors. Three of them (rac-4, rac-5, and rac-6) showed good enzyme inhibition (Ki 117.5, 90.62, and 77.30 µM, respectively), with a pattern of competitive inhibition type supported by in silico and in vitro experiments, being the rac-6 derivative the best inhibitor. The structural analysis showed that the presence of the ethyl ester group in the structure favors inhibition, likewise, the presence of double bonds increases the affinity of the inhibitor for the enzyme, so these new pyrrolo[2,1-a]isoindol-5-ones derivatives might be helpful for the treatment of Alzheimer’s disease.

Simultaneous and sialic acid linkage-specific N- and O-linked glycan analysis by ester-to-amide derivatization.

Characterization of O-glycans linked to serine or threonine residues in glycoproteins has mostly been achieved using chemical reaction approaches because there are no known O-glycan-specific endoglycosidases. Most O-glycans are modified with sialic acid residues at the non-reducing termini through various linkages. In this study, we developed a novel approach for sialic acid linkage-specific O-linked glycan analysis through lactone-driven ester-to-amide derivatization combined with non-reductive β-elimination in the presence of hydroxylamine. O-glycans released by non-reductive β-elimination were efficiently purified using glycoblotting via chemoselective ligation between carbohydrates and a hydrazide-functionalized polymer, followed by modification of methyl or ethyl ester groups of sialic acid residues on solid-phase. In-solution lactone-driven ester-to-amide derivatization of ethyl-esterified O-glycans was performed, and the resulting sialylated glycan isomers were discriminated by mass spectrometry. In combination with PNGase F digestion, we carried out simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses of a model glycoprotein and human cartilage tissue. This novel glycomic approach will facilitate detailed characterization of biologically relevant sialylated N- and O-glycans on glycoproteins.

Synthesis and Evaluation of Self-Assembling Properties of 3-(3,5-Difluoro-3,5-bis((alkoxy)carbonyl)-2,6-dioxoheptan-4-yl)-1-methylpyridin-1-ium Iodides

A synthesis of 3-(3,5-difluoro-3,5-bis((alkoxy)carbonyl)-2,6-dioxoheptan-4-yl)-1-methylpyridin-1-ium iodides with ethyl or nonyl ester groups at positions 3 and 5 was performed. Treatment of the corresponding 2’,6’-dimethyl-1’,4’-dihydro-[3,4’-bipyridine]-3’,5’-dicarboxylates with Selectfluor® followed by quaternization of pyridine moiety in the obtained dialkyl 2,4-diacetyl-2,4-difluoro-3-(pyridin-3-yl)pentanedioates with methyl iodide gave the desired 3-(3,5-difluoro-3,5-bis((alkoxy)carbonyl)-2,6-dioxoheptan-4-yl)-1-methylpyridin-1-ium iodides. This type of compound would be useful as synthetic lipids for further development of the delivery systems. The obtained target compounds were fully characterized by 1H NMR, 19F NMR, 13C NMR, HRMS, IR and UV data. The estimation of self-assembling properties and characterization of the nanoparticles obtained by ethanol solution injection in an aqueous media were performed by dynamic light scattering (DLS) measurements. DLS measurement data showed that 3-(3,5-difluoro-3,5-bis((nonyloxy)carbonyl)-2,6-dioxoheptan-4-yl)-1-methylpyridin-1-ium iodide created liposomes with the average diameter of 300–400 nm and polydispersity index (PDI) value around 0.30–0.40, while 3-(3,5-difluoro-3,5-bis((ethyloxy)carbonyl)-2,6-dioxoheptan-4-yl)-1-methylpyridin-1-ium iodide formed a heterogeneous sample with PDI value 1, which was not prospective for delivery system development.

Study on oxidation and pyrolysis of carbonate esters using a micro flow reactor with a controlled temperature profile. Part I: Reactivities of dimethyl carbonate, ethyl methyl carbonate and diethyl carbonate

Carbonate esters such as dimethyl carbonate (DMC), ethyl methyl carbonate (EMC) and diethyl carbonate (DEC) are widely used as electrolyte solvents in a lithium-ion battery (LIB) and are considered as one of potential fire causes. This study investigates a difference in gas-phase reactivities of DMC, EMC and DEC. Species measurements for oxidation (equivalence ratio of 1.0) and pyrolysis of DMC and DEC at maximum wall temperatures of Tw,max = 700–1300 K and atmospheric pressure were performed using a gas chromatograph connected to a micro flow reactor with a controlled temperature profile (MFR). Measured mole fractions of C2H4 and CO2 in the DEC case started increasing at a low temperature (Tw,max = 750 K), while those of CH4 and CO2 in the DMC case started increasing at an intermediate temperature (Tw,max = 1050 K). Gas-phase reactivities of the three carbonate esters were found to be DMC < EMC ≈ DEC through observation of their weak flames. Computational species and heat release rate profiles of DEC showed a three-stage reaction: thermal decomposition, oxidation of decomposition products to CO and CO oxidation to CO2. This three-stage reaction of DEC is distinct from the one driven by low-temperature oxidation observed with n-heptane and DME in earlier studies. Rate of production analysis indicated that principal fuel consumption reactions of DMC were H-atom abstraction reactions and that of DEC was a thermal decomposition reaction producing C2H4. Based on reaction path analysis of DEC oxidation, initial-stage reactions produced few active radicals at the low temperature region. The reactivity difference between DMC and DEC is, therefore, mainly driven by the difference in the primary fuel consumption reactions that relies on fuel molecular structure. Considering the existence of ethyl ester group in EMC, a dominant EMC consumption reaction would be similar to DEC.

Anti-tubercular activity and molecular docking studies of indolizine derivatives targeting mycobacterial InhA enzyme

A series of 1,2,3-trisubstituted indolizines (2a–2f, 3a–3d, and 4a–4c) were screened for in vitro whole-cell anti-tubercular activity against the susceptible H37Rv and multidrug-resistant (MDR) Mycobacterium tuberculosis (MTB) strains. Compounds 2b–2d, 3a–3d, and 4a–4c were active against the H37Rv-MTB strain with minimum inhibitory concentration (MIC) ranging from 4 to 32 µg/mL, whereas the indolizines 4a–4c, with ethyl ester group at the 4-position of the benzoyl ring also exhibited anti-MDR-MTB activity (MIC = 16–64 µg/mL). In silico docking study revealed the enoyl-acyl carrier protein reductase (InhA) and anthranilate phosphoribosyltransferase as potential molecular targets for the indolizines. The X-ray diffraction analysis of the compound 4b was also carried out. Further, a safety study (in silico and in vitro) demonstrated no toxicity for these compounds. Thus, the indolizines warrant further development and may represent a novel promising class of InhA inhibitors and multi-targeting agents to combat drug-sensitive and drug-resistant MTB strains.

Structural, spectroscopic, and photochemical study of ethyl propiolate isolated in cryogenic argon and nitrogen matrices.

Ethyl propiolate (HC≡CCOOCH2CH3, EP) was studied experimentally by infrared spectroscopy in argon and nitrogen cryomatrices (15K) and by quantum chemical calculations (at the DFT(B3LYP) and MP2 levels of theory). Calculations predict the existence of four conformers: two low-energy conformers (I and II) possessing the carboxylic moiety in the cis configuration (O=C-O-C dihedral equal to ~0°) and two higher-energy trans forms (O=C-O-C dihedral equal to ~180°; III and IV). The conformation of the ethyl ester group within each pair of conformers is either anti (C-O-C-C equal to 180°; in conformers I and III) or gauche (C-O-C-C equal to ±86.6° in II, and±92.5° in IV). The two low-energy cis conformers (I and II) were predicted to differ in energy by less than 2.5kJmol-1 and were shown to be present in the studied cryogenic matrices. Characteristic bands for each one of these conformers were identified in the infrared spectra of the matrix-isolated compound and assigned taking into account the results of normal coordinate analysis, which used the geometries and harmonic force constants obtained in the DFT calculations. The two trans conformers (III and IV) were estimated to be 17.5kJmol-1 higher in energy than the conformational ground state (form I) and were not observed experimentally. The unimolecular photochemistry of matrix-isolated EP (in N2 matrix) was also investigated. In situ irradiation with UV light (λ>235nm) leads mainly to decarbonylation of the compound, with generation of ethoxyethyne, which in a subsequent photoreaction generates ketene (plus ethene).

Antiproliferative and antiinflammatory coxib-combretastatin hybrids suppress cell cycle progression and induce apoptosis of MCF7 breast cancer cells.

In our study, some newly synthesized aryl-substituted pyrazole derivatives mimicking cis-diphenylethylene scaffold of two apoptotic inducing agents celecoxib and combretastatin A-4 were found to have strong antiproliferative as well as antiinflammatory activities. Among these coxib-combretastatin hybrids, two lead compounds 8 and 6c simultaneously inhibited prostaglandin E2 (PGE2) production in LPS-activated murine macrophage RAW 264.7 cells and suppressed cell cycle progression of MCF7 cells at G2/M or G0/G1 phases, but only compound 8 induced apoptosis via caspase-3 activation. Both the lead compounds showed good docking energies with both protein targets COX-2 and tubulin in the molecule interaction modeling. The cis-diphenylethylene scaffold of celecoxib or combretastatin A-4 as well as functional groups such as the ethyl ester group and the sulfonamide could be considered as potential key features for the dual activity of studied compounds meanwhile the trimethoxybenzene remained the crucial characterization of the newly derived compounds of combretastatins.

Synthesis and Molecular Docking Studies of Novel Triazole Derivatives as Antioxidant Agents

A series of 1,2,4-triazole and 1,2,4- thiadiazole derivatives were prepared starting from ethyl 4-(3-methyl-5-oxo-1,5-dihydro-4H-1,2,4-triazol-4-yl)benzoate. Firstly, both ethyl ester groups were simultaneously transformed into hydrazide groups, then into thiosemicarbazide groups using both microwave- assisted and conventional methods. The latter products were interacted with NaOH and H2SO4 to form ring assemblies containing two 1,2,4-triazole and 1,3,4-thiadiazole fragments, respectively. Antioxidant activities of the synthesized compounds were determined with CUPRAC, ABTS, and DPPH assays. Most of the compounds showed significant antioxidant activity and especially, compound 3 exhibited very good SC50 value for DPPH method and compound 3, 4a, 5a exhibited very high scavenging activity to the ABTS method. In addition, the in silico analysis was carried out with the synthesized derivatives to understand the mode of interaction with superoxide dismutase (SOD) and human tyrosine kinase using docking protocols in order to find out the most active antioxidant drug having high inhibitory activity in cancer.

Novel "ruthenium cyclopentadienyl"-peptide conjugate complexes against human FGFR(+) breast cancer.

In this work we explored the possibility of improving the selectivity of a cytotoxic Ru complex [RuCp(PPh3)(2,2'-bipy)][CF3SO3] (where Cp = η5-cyclopentadienyl) TM34 towards FGFR(+) breast cancer cells. Molecular dynamics (MD) simulations of TM34 in a phosphatidylcholine membrane model pinpointed the cyclopentadienyl group as a favorable derivatization position for the peptide conjugation approach. Three new Ru(ii) complexes presenting a functionalized η5-cyclopentadienyl were synthesized, namely [Ru(η5-C5H4COOH)(2,2'-bipy)(PPh3)][CF3SO3] (TM281) and its precursors, [Ru(η5-C5H4COOCH2CH3)(η2-2,2'-bipy)(PPh3)][CF3SO3] (3) and [Ru(η5-C5H4COOCH2CH3)(PPh3)2Cl] (2). Complex TM281 was prepared by the hydrolysis of the ethyl ester group appended to the η5-cyclopentadienyl ligand of complex 3 with K2CO3 in water/acetonitrile, followed by mild protonation using an ion exchange resin. The newly synthesized complexes were fully characterized by NMR, FTIR and UV-vis spectroscopic techniques. Also, electrochemical studies were carried out by means of cyclic voltammetry in order to evaluate the stability of the compounds. Single crystal X-ray diffraction studies were carried out for compounds 3 and TM281 which crystallized in the monoclinic system, space group P21/n. The unprecedented synthesis and characterization of three half-sandwich ruthenium(ii)-cyclopentadienyl peptide conjugates and their preliminary biological evaluation against human FGFR(+) and FGFR(-) breast cancer cells are also reported.

Novel acrylic monomers for organic photovoltaics encapsulation

Cheap and efficient encapsulation methods are needed for successful commercialization of organic photovoltaics (OPV). Application of epoxy or acrylic UV-curable adhesives is a fast and scalable way to encapsulate organic solar cells. Despite lower barrier properties, acrylates have some benefits over epoxies such as higher cure speed, better adhesion to various substrates, lower viscosity and increased mechanical flexibility. In this work commercial and novel acrylic monomers were applied for encapsulation of OPV. It was found that monomers with phenyl ethyl ester group can have very high adhesion to polyethylene terephthalate (PET), good barrier properties and good compatibility with a layer stack of OPV devices.

Control of Excited-State Supramolecular Assembly Leading to Halide Photorelease.

Ground- and excited-state control of halide supramolecular assembly was achieved through the preparation of a series of ester- and amide-functionalized ruthenium polypyridyl complexes in CH2Cl2. Hydrogen-bonding amide and alcohol groups on the receptor ligand were found to direct interactions with halide, while halide association with the ethyl ester groups was not observed. The various functional groups on the receptor ligands tuned the ground-state equilibrium constants over 2 orders of magnitude (1 × 105 to 1 × 107 M-1), and the fractional contribution of each hydrogen-bond donor to the total equilibrium constant was determined. Pulsed-laser excitation of the complexes resulted in excited-state localization on the ester- or amide-functionalized ligands. In the case where the excited state was oriented toward an associated halide ion (the amide complexes), an 80 ± 10 meV Coulombic repulsion was induced that lowered the excited-state equilibrium constant ( K*eq) and resulted in halide photorelease. The rate constants for excited-state halide release ( k*21) were determined, and the values varied based on the functional groups present in the receptor ligand. Complexes with more hydrogen-bonding donors had smaller rate constants for halide photorelease. In a complex without a specific receptor ligand, the excited-state dipole was not oriented toward the associated halide, and the excited state was therefore found to have a larger equilibrium constant for halide association than the ground state.

Synthesis and Antibacterial Evaluation of Hydrazone Derivatives Bearing 6-Chlorothieno[3,2-c]pyridine Moiety

The present investigation describes the overall preparation of 6-chlorothieno[3,2-c]pyridine-2-carbohydrazide-hydrazone subsidiaries (7a-r) from industrially accessible ethyl-4,6-dichloronicotinate as starting material. The synthesis of these derivatives involve some prominent reactions such as (i) NaBH4 reduction of ethyl ester group (ii) MnO2 oxidation of 1º alcohol (iii) cyclization of aldehyde with ethylmercapto acetate leading to thieno[3,2-c]pyridine ring (iv) hydrazinolysis of the ethyl group (v) condensation of selected aldehydes with 6-chlorothieno[3,2-c]pyridine-2-carbohydrazide leading to the desired 6-chlorothieno[3,2-c]pyridine-2-carbohydrazide-hydrazone derivatives (7a-r). The structure of the derivatives was characterized by elemental analysis, NMR, infrared and mass spectroscopic analysis. These compounds were screened for their antibacterial property towards Gram positive and Gram negative bacterial strains using agar diffusion method with reference to norfloxacin as reference antibiotic.

The Chemoattractant Glorin Is Inactivated by Ester Cleavage during Early Multicellular Development of Polysphondylium pallidum.

Among the amoebozoan species capable of forming fruiting bodies, the dictyostelid social amoebae stand out since they form true multicellular organisms by means of single cell aggregation. Upon food depletion, cells migrate across gradients of extracellular signals initiated by cells in aggregation centers. The model species that is widely used to study multicellular development of social amoebae, Dictyostelium discoideum, uses cyclic adenosine monophosphate (cAMP) as a chemoattractant to coordinate aggregation. Molecular phylogeny studies suggested that social amoebae evolved in four major groups, of which groups 1 and 2 are paraphyletic to groups 3 and 4. During early development, intercellular communication with cAMP appears to be restricted to group 4 species. Cells of group 1 and 2 taxa do not respond chemotactically to extracellular cAMP and likely use a dipeptide chemoattractant known as glorin ( N-propionyl-γ-L-glutamyl-L-ornithin-δ-lactam-ethylester) to regulate aggregation. Directional migration of glorin-responsive cells requires the periodic breakdown of the chemoattractant. Here, we identified an extracellular enzymatic activity (glorinase) in the glorin-responsive group 2 taxon Polysphondylium pallidum leading to the inactivation of glorin. We determined the inactivation mechanism to proceed via hydrolytic ethyl ester cleavage of the γ-glutamyl moiety of glorin. Synthetic glorinamide, in which the ethyl ester group was substituted by an ethyl amide group, had glorin-like biological activity but was resistant to degradation by glorinase. Our observations pave the way for future investigations toward an ancient eukaryotic chemotaxis system.