L-cysteine Ethyl Ester Hydrochloride Research Articles

Anti-Inflammatory Actions of Expectorants in a Rat Carrageenan-Induced Footpad Edema Model.

S-Carboxymethyl-L-cysteine (SCMS) exhibits sputum-regulating and anti-inflammatory actions. Previous studies reported the anti-inflammatory effects of SCMS on chronic inflammatory diseases, but no study has examined these effects on acute inflammatory diseases. In this study, we investigated the anti-inflammatory effects of SCMS in a rat carrageenan-induced footpad edema model, which is routinely used as an acute inflammation model. Expectorants were administered to rats with footpad edema induced by subcutaneously administering 1%λ-carrageenan to the footpad of the left posterior limb, and the dose dependency of the anti-inflammatory effects was evaluated. As a result, even when the dose of SCMS was increased to 400 mg/kg, there were no inhibitory effects on edema. Furthermore, we examined the inhibitory effects of other expectorants (ambroxol hydrochloride, N-acetyl-L-cysteine, L-cysteine ethylester hydrochloride, and L-cysteine methylester hydrochloride), which were reported to exhibit anti-inflammatory effects on chronic inflammation, on edema. However, none of these expectorants inhibited edema.

Synthesis, characterization and evaluation of hyaluronic acid-based polymers for nasal delivery

Epidemiological research has found that between 5 and 12 percent of the population suffers from chronic rhinosinusitis. Patients are dealing with local side effects such as nasal dryness, sporadic sneezing, and nasal pain in addition to the inflammation. The aim of this study was to synthesize a polymer based on hyaluronic acid in order to provide lubrication combined with a ligand leading to a covalent binding on the nasal mucosa. Hyaluronic acid (HA) was modified with L-cysteine ethyl ester hydrochloride (CYS) via amid bond formation. Ellman's assay, together with spectroscopic techniques like IR and 1H NMR, confirmed that HACys had been successfully synthesized. It was demonstrated that HACys is safe for administration on the nasal mucosa. The mucoadhesive potential was determined by 3.26-fold with the rotating cylinder assay and 1.4-fold in terms of bioadhesive examination, respectively. Further, the stability of the modified polymer was improved by 7.6-fold compared to the unmodified polymer. Spraying the formulation on the nasal mucosa, the residence time of a model drug was 1.74-fold prolonged at the site of action compared to unmodified polymer. In light of these findings, modified hyaluronic acid (HACys) displayed compelling properties such as lubricity, targeted application, long-lasting effect, and safety and therefore could be an excellent candidate for nasal application.

Preparation and in vivo toxicity study of allantoin incorporated hyaluronic acid-L-cysteine oral solution: A future treatment for mucositis

Background: Thiolated hyaluronic acid (HA) with interesting properties, such as muco-adhesiveness, enzyme inhibitory, permeation enhancing, and release controlling properties can be applied for drug delivery in various diseases like mucositis. The purpose of this study was to evaluate the stability and toxicity of thiol modified HA by the aid of L-cysteine ethyl ester hydrochloride (Cys) named (HA-Cys) and allantoin (Alla) incorporated HA-Cys (HA-Cys-Alla) to reveal their potential for the future treatment of mucositis. Methods: The HA modification and drug incorporation were investigated using FTIR spectroscopy. The evaluation of in vitro cytotoxicity on Caco-2 cell line by means of MTT assay and in vivo toxicity by measuring the hematological and biochemical parameters in rats were performed. The appearance stability of HA-Cys and HA-Cys-Alla was evaluated at room and refrigerator temperatures over time. In addition, the stability of HA-Cys and HA-Cys-Alla subjected to heating and cooling, freeze-thaw, centrifugal forces, as well as the pH stability under the above-mentioned conditions were also investigated. Results: The results indicated that the synthesized HA-Cys and HA-Cys-Alla with pseudo-plastic rheological behavior demonstrated excellent stability at refrigerator temperature. Although HA-Cys showed good stability, the HA-Cys-Alla revealed color change at room temperature. Moreover, despite no much resistance of HA-Cys and HA-Cys-Alla against the heating-cooling test, the samples exhibited good resistance against freeze-thaw and centrifugal forces. Also, convenient pH stability and high in vitro and in vivo biocompatibility were observed. Conclusions: The low in vitro and in vivo toxicity and convenient stability of HA-Cys-Alla has introduced it as a proper candidate for future clinical applications.

Hyaluronic acid-functionalized redox responsive immunomagnetic nanocarrier for circulating tumor cell capture and release

Detection of circulating tumor cells (CTCs) in peripheral blood holds significant insights for cancer diagnosis, prognosis evaluation, and precision medicine. To efficiently capture and release CTCs with high viability, we reported the development of hyaluronic acid (HA)-functionalized redox responsive immunomagnetic nanocarrier (Fe3O4@SiO2-SS-HA). First, Fe3O4 nanoparticles were prepared and modified with tetraethyl orthosilicate (TEOS), 3-mercaptopropyltrimethoxysilane (MPTMS) and 2,2′-dithiodipyridine (DDPy) to form the magnetic substrate (Fe3O4@SiO2-SSPy). Modified with targeted segment HA-functionalized L-cysteine ethyl ester hydrochloride (HA-Cys) via disulfide exchange reaction, the Fe3O4@SiO2-SS-HA was formed. The nanocarrier with prominent magnetic property, targeting ligand, and redox-sensitive disulfide linkages was able to specially capture MCF-7 cells with an efficiency of 92% and effectively release captured cells with an efficiency of 81.4%. Furthermore, the Fe3O4@SiO2-SS-HA could successfully be used for the capture of MCF-7 cells, and the captured cells could be diferntiated from the blood cells. Almost all of released tumor cells kept good viability and a robust proliferative capacity after being re-cultured. It is likely that the as-prepared nanocarrier will serve as a new weapon against CD44 receptor-overexpressed cancer cells.

FTIR and Raman analysis ofl-cysteine ethyl ester HCl interaction with dipalmitoylphosphatidylcholine in anhydrous and hydrated states

Interactions of l-cysteine ethyl ester hydrochloride (CE), a bioactive cysteine derivative, with dipalmitoylphosphatidylcholine (DPPC) were investigated. To gain a deeper insight into analyzing l-cysteine ethyl ester HCl interaction with liposomes of DPPC in anhydrous and hydrated states, we performed experimental studies by infrared (Fourier transform infrared spectroscopy) and Raman spectroscopies. The results revealed that the interaction of CE with the phospholipid head groups was the same in absence or presence of water. In both states, the wavenumber of the PO2− group and CN bond of the choline group decreased. This behavior can be ascribed to the replacement of hydration water and binding to the phosphate group. In the Raman spectrum results for the anhydrous and gel states, the SH stretching band of the CE shifted to lower frequencies with a decrease in its force constant. Biologically active lipophilic molecules such as CE should be studied in terms of their interaction with lipid bilayers prior to the development of advanced lipid carrier systems such as liposomes. The results of these studies provide information on membrane integrity and physicochemical properties that are essential for the rational design of lipidic drug delivery systems. Copyright © 2015 John Wiley & Sons, Ltd.

Vibrational and Structural Behavior of l-Cysteine Ethyl Ester Hydrochloride in the Solid State and in Aqueous Solution

The aim of this work is to evaluate the vibrational and structural properties of l-cysteine ethyl ester hydrochloride (CE), and its electronic behavior mainly in relation to the action of the thiol and amine groups at different degrees of solvation. The crystal structure of CE was determined at room temperature by X-ray diffraction methods. Infrared and Raman spectra were collected to compare the behavior of different functional groups in the molecule, both in the solid phase and in aqueous solution. Its UV and circular dichroism spectra were also measured in aqueous solution. The influence of an aqueous environment on the CE spectra was simulated by means of implicit (polarizable continuum model) and explicit (molecular dynamics, solute-solvent clusters) methods. Calculations in explicit and continuous solvent are of interest to explain the behavior of bioavailable sites in this medium. The study was completed by natural bond orbital analysis to determine the presence of hyperconjugative interactions.

Epitaxial growth of colloidal hydrophilic lattice matched HgTe/CdTe core/shell nanocrystals for UV luminescence

The present work reports a bottom up approach to synthesize water dispersed and highly luminescent hydrophilic l-cysteine ethyl ester hydrochloride (LEEH) capped and lattice matched HgTe/CdTe core/shell nanoparticles (NPs). The LEEH concentration was varied to optimize the luminescent properties of the core/shell NPs by controlling the particle size and its size distribution. FTIR measurements confirm the LEEH capping to the core/shell nanostructures. Transmission electron microscopy (TEM) measurements identify the HgTe, core size as 2.0 nm and that of the shell, epitaxially grown over the core has the thickness as 0.8 nm which corresponds to 2.1 monolayers of CdTe for an optimum LEEH concentration of 4.8 mM. The absorption studies showed excitonic absorption at 293 nm for the optimized core/shell NPs. More than three fold increase of fluorescence (FL) yield in case of the core/shell structure compared to the core has been observed in this study. X-ray diffraction and micro-Raman studies do not show an alloying effect. The crystalline sizes estimated both from X-ray diffraction and HRTEM are found to be comparable.

Facile synthesis of cysteine and triethanolamine capped CdTe nanoparticles

Cysteine and triethanolamine capped CdTe nanoparticles have been synthesized using a simple aqueous solution based method. This method involves the reaction of tellurium powder with sodium borohydride (NaBH4) in water to produce telluride ions (Te2−), followed by the simultaneous addition of an aqueous solution of cadmium chloride or other cadmium source (acetate, carbonate and nitrate) and solution of l-cysteine ethyl ester hydrochloride or triethanolamine. The effect of capping agent on the size, structure and morphology of the as-synthesized nanoparticles was investigated. The particles were characterized using optical spectroscopy, transmission electron microscopy (TEM), high-resolution TEM (HRTEM), X-ray diffraction (XRD) and Fourier transform infrared (FT-IR) spectroscopy.

Surface-Enhanced Raman Scattering Spectroscopy of Explosive 2,4-Dinitroanisole using Modified Silver Nanoparticles

2,4-Dinitroanisole (DNAN) is being used as a replacement for 2,4,6-trinitrotoluene (TNT) as a less-sensitive melt-cast medium explosive than TNT. In this paper, we studied the surface-enhanced Raman spectroscopy (SERS) analysis of DNAN using Ag nanoparticles (AgNPs) modified by L-cysteine methyl ester hydrochloride. Due to the formation of a Meisenheimer complex between DNAN and the modifier, the modified AgNPs can detect 20 μg/L (0.2 ng) and 0.1 mg/L (1 ng) DNAN in deionized water and aged tap water, respectively. Three other chemicals (L-cysteine, N-acetyl-L-cysteine, and L-cysteine ethyl ester hydrochloride) were used as AgNPs modifiers to study the mechanism of the SERS of DNAN. It was confirmed that the amino group of L-cysteine methyl ester hydrochloride was the active group and that the methyl ester group significantly contributed to the high SERS sensitivity of DNAN. In order to further test the mechanism of Meisenheimer complex formation, the effect of anions and cations present in natural water on the SERS of DNAN was studied. It was found that CO(3)(2-), Cl(-), and K(+) at 100 mg/L did not negatively affect the SERS of 10 mg/L DNAN, while SO(4)(2-), Na(+), Mg(2+), and Ca(2+) at 100 mg/L significantly quenched the SERS of 10 mg/L DNAN. The negative effect of the bivalent cations could be offset by SO(4)(2-).

Size quantization effect in highly stable UV emitting HgTe nanoparticles: Structure and optical properties

We report a simple one pot aqueous chemical synthesis route to fabricate very small and highly stable HgTe nanoparticles (NPs) capped with L-cysteine ethyl ester hydrochloride (LEEH). The LEEH concentration has found to be critical for desired size NP synthesis. Structural analyses by grazing angle x-ray diffraction and high resolution electron microscopy studies indicate HgTe NPs to exhibit a fcc phase with ⟨111⟩ prominent reflection having monodispersed NP size of around 2.0 nm. A strong size quantization effect marked by a prominent excitonic absorption at 4.436 eV blueshifted by 4.586 eV from the bulk band gap value has been observed in their optical absorption studies. A strong and narrow Gaussian fluorescence emission at 3.3 eV has been observed for 2.0 nm NP size whose width is being narrowed down with increasing LEEH concentration. The strong UV range absorption and emission have been observed for the first time in HgTe NPs.

A novel one-pot route for the synthesis of water-soluble cadmium selenide nanoparticles

A novel, facile one-pot synthetic route to highly water dispersible and potentially biocompatible CdSe nanoparticles is reported. The monodispersed CdSe particles are passivated by cysteine, with water being the solvent. This route involves the reaction of selenium powder with sodium borohydride to produce selenide ions, followed by the addition of a cadmium salt and l-cysteine ethyl ester hydrochloride. The nanoparticles formed show quantum confinement fluorescing in the blue region. Fourier transform infrared spectroscopy study shows that CdSe nanoparticles are capped through mercapto group of the amino acid cysteine whilst its free amino and carboxylate groups make it amenable to bioconjugation establishing the possibility of using these as fluorescent biomarkers. High-resolution transmission electron spectroscopy images of these materials show well-defined, crystalline nanosized particles. Energy dispersive spectroscopy spectra confirm the presence of the corresponding elements.

Synthesis and in vitro evaluation of thiolated hyaluronic acid for mucoadhesive drug delivery

It was the aim of this study to synthesize and characterize a novel hyaluronic acid-cysteine ethyl ester (HA-Cys) conjugate providing improved mucoadhesive properties and a significantly lowered biodegradation rate. Mediated by carbodiimide and N-hydroxysuccinimide, l-cysteine ethyl ester hydrochloride was covalently attached to hyaluronic acid (HA, hyaluronan) via the formation of an amide bond. The adhesive properties of HA-Cys conjugates were evaluated in vitro on a freshly excised porcine mucosa via the rotating cylinder method. The cohesive properties of the resulting conjugates were evaluated by oxidation experiments. Biodegradability studies were carried out by viscosity measurements and spectrophotometric assays. Release studies were performed with fluorescein isothiocyanate-dextrans (FD) as model compounds. The obtained conjugate displayed 201.3 ± 18.7 μmol immobilized free thiol groups and 85.7 ± 22.3 μmol disulfide bonds per gram polymer. Results from the rotating cylinder method showed more than 6.5-fold increase in the adhesion time of HA-Cys versus unmodified HA. In aqueous solutions, the obtained conjugate demonstrated improved cohesive properties. The hydrolysis degree of HA-Cys was lower compared with the corresponding unmodified HA in the framework of viscosity experiments. In addition, the cross-linking process via disulfide bonds additionally reduced the rate of degradation of the new derivative. Cumulative release studies out of matrix tablets comprising HA-Cys and the model compound FD demonstrated a sustained drug release for more than 12 h due to in situ formation of inter- and intramolecular disulfide bonds in the thiomer matrix. According to the results of the present study, this novel thiolated polymer seems to represent a promising multifunctional excipient for the development of various drug delivery systems.

Developing iron nitrosyl complexes as NO donor prodrugs

A novel class of water-soluble iron nitrosyl complexes has been developed for use as NO donor prodrugs. To elaborate these NO prodrugs various water-soluble ligands were used such as P(CH2OH)3, 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane (PTA), 1,2-bis[bis(hydroxymethyl)phosphino]ethane (HMPE), 1,2-bis[bis(hydroxymethyl)phosphino]benzene (TMBz), cysteamine, cysteamine hydrochloride, L-cysteine ethyl ester hydrochloride (LCEE) and pyrimidine-2-thiol (pyrim). The mononuclear complexes Fe(NO)2P(CH2OH)3Cl , Fe(NO)2(P(CH2OH)3)2, Fe(NO)2(PTA)2, Fe(NO)2HMPE , Fe(NO)2TMBz , [Fe(NO)2pyrimI] , [Fe(NO)3P(CH2OH)3][X] (X=PF6, SbF6, BF4) and the dinuclear species [Fe(NO)2S(CH2)2NH3Cl]2, [Fe(NO)2S(CH2)2NH3I2] , [Fe(NO)2LCEE]2 and [Fe(NO)2pyrim]2 were obtained. Complexes , , , , , , and are water-soluble. , and were identified as nitroxyl and , , , and as nitric oxide donors by applying an EPR NO-trap assay. To determine the amount of nitric oxide which was released from the nitric oxide donors, an additional electrochemical methodology was used. The equilibrium release or the trapping concentration of NO was also studied by a UV-vis method, which allowed the rate constant of NO release to be determined.

The solid-state molecular structure of the S-nitroso derivative of l-cysteine ethyl ester hydrochloride

Nitrosation of protein sulfhydryl groups to form thionitrites (S-nitrosothiols) has been reported to be important in the biochemistry of nitric oxide. Such S-nitrosation of protein thiol residues has been shown to alter the function of some proteins. In this brief communication, we report the X-ray crystal structure of S-nitroso-L-cysteine ethyl ester hydrochloride. Two rotamers with respect to the NCCS moiety are present in the crystal: the major rotamer is in the gauche+ conformation, and the minor rotamer is in the rare anti (trans, antiperiplanar) conformation for a cysteinyl compound. Importantly, the CSNO groups for both rotamers are in the syn (cis, synperiplanar) form. To the best of our knowledge, this is the first reported high-resolution solid-state structure of an S-nitroso derivative of a cysteine or cysteinyl-containing compound.

Synthesis of N‐Substituted Thiazolidines and Dihydrobenzothiazoles.

Ethyl (4R)-3-(1H-1,2,3-benzotriazol-1-ylmethyl)-1,3-thiazolane-4-carboxylate (6) and 1-[1,3-benzothiazol-3(2H)-ylmethyl]-1H-1,2,3-benzotriazole (8) were readily prepared by reactions of L-cysteine ethyl ester hydrochloride and 1-aminothiophenol with benzotriazole and formaldehyde, respectively. Chiral thiazolidine esters 7a-c were obtained by reactions of intermediate 6 with organozinc derivatives. Nucleophilic substitutions of 8 with Grignard reagents gave N-substituted dihydrobenzothiazoles 9a-c.

Synthesis of N-Substituted Thiazolidines and Dihydrobenzothiazoles

Ethyl (4R)-3-(1H-1,2,3-benzotriazol-1-ylmethyl)-1,3-thiazolane-4-carboxylate (6) and 1-[1,3-benzothiazol-3(2H)-ylmethyl]-1H-1,2,3-benzotriazole (8) were readily prepared by reactions of l-cysteine ethyl ester hydrochloride and 1-aminothiophenol with benzotriazole and formaldehyde, respectively. Chiral thiazolidine esters 7a-c were obtained by reactions of intermediate 6 with organozinc derivatives. Nucleophilic substitutions of 8 with Grignard reagents gave N-substituted dihydrobenzothiazoles 9a-c.

High-Field Chlorine NMR Spectroscopy of Solid Organic Hydrochloride Salts: A Sensitive Probe of Hydrogen Bonding Environment

A series of organic hydrochloride salts has been investigated using solid-state 35Cl and 37Cl NMR spectroscopy at applied magnetic field strengths of 9.4 and 18.8 T. Magic-angle spinning, static Hahn-echo, and quadrupolar Carr−Purcell Meiboom−Gill (QCPMG) echo experiments have been applied to investigate the chlorine electric field gradient (EFG) and chemical shift (CS) tensors for l-tyrosine hydrochloride, l-cysteine methyl ester hydrochloride, l-cysteine ethyl ester hydrochloride, quinuclidine hydrochloride, and tris sarcosine calcium chloride. Chlorine-35 nuclear quadrupolar coupling constants for these compounds range from 2.23 to 5.25 MHz, and isotropic chemical shifts range from approximately 9 to 53 ppm relative to the chloride ion in aqueous solution. The results demonstrate the feasibility and benefits of high-field 35/37Cl NMR studies of organic chloride salts. A discussion of the data in the context of the known X-ray or neutron diffraction structures for these compounds suggests that the chlor...

Synthesis of a novel prostaglandin containing heteroatoms in the ring cyclopentane

A novel prostaglandin analogue, n-heptyl-4-(3-hydroxy- trans-1-octenyl)-1,3-thiazolidin-2-thione, containing heteroatoms in the ring has been synthesized. The key step in the synthesis was the preparation of the five-membered ring starting from of l-cysteine ethyl ester hydrochloride.

Amino acid induced iron-sulfur cluster interconversions studied by 1H NMR and Mössbauer spectroscopies

The cluster [Fe 2S 2(SBu t) 4] 2− on reacting with L-cysteine ethyl ester hydrochloride (HCys-OEt · HCl) converts to the tetranuclear cysteinate-bound cluster [Fe 4S 4(Cys-OEt · HCl) 4] 2−. In contrast, the dinuclear tyrosinate-bound cluster [Fe 2S 2(Tyr-OMe) 4] 2− (HTyr-OMe = L-tyrosine methyl ester) can be prepared from either [Fe 2S 2(SBu t) 4] 2−, or as a decomposition product in the reaction of hexanuclear [Fe 6S 6Cl 6] 3− with NaTyr-OMe. Under appropriate conditions the hexanuclear tyrosinate-bound cluster [Fe 6S 6(Tyr-OMe) 6] 3− can be isolated. The thermal stability of clusters [Fe 6S 6(XR) 6] 3− (X=S, O) toward conversion to tetranuclear [Fe 4S 4(XR) 4] 2− lies in the order tyrosinate-≥phenolate->thiophenolate-bound cluster. 1H NMR and Mössbauer spectroscopies are used to unequivocally identify the products.

(η 5-cyclopentadienyl)Fe(CO) 2-complex of maleimide anion: An organometallic carbonyl probe for biomolecules containing HS groups

Synthesis of (η 5-cyclopentadienyl)Fe(CO) 2(η 1-N-maleimidato) complex and its reaction with L-cysteine ethyl ester hydrochloride and glutathione are reported. This reaction enables introduction of a metal carbonyl probe into biomolecules containing HS groups.