Cysteine Ethyl Ester Research Articles

Synthesis and Characterization of Thiolated Nanoparticles Based on Poly (Acrylic Acid) and Algal Cell Wall Biopolymers for the Delivery of the Receptor Binding Domain from SARS-CoV-2.

The COVID-19 pandemic required great efforts to develop efficient vaccines in a short period of time. However, innovative vaccines against SARS-CoV-2 virus are needed to achieve broad immune protection against variants of concern. Polymeric-based particles can lead to innovative vaccines, serving as stable, safe and immunostimulatory antigen delivery systems. In this work, polymeric-based particles called thiolated PAA/Schizo were developed. Poly (acrylic acid) (PAA) was thiolated with cysteine ethyl ester and crosslinked with a Schizochytrium sp. cell wall fraction under an inverse emulsion approach. Particles showed a hydrodynamic diameter of 313 ± 38 nm and negative Zeta potential. FT-IR spectra indicated the presence of coconut oil in thiolated PAA/Schizo particles, which, along with the microalgae, could contribute to their biocompatibility and bioactive properties. TGA analysis suggested strong interactions between the thiolated PAA/Schizo components. In vitro assessment revealed that thiolated particles have a higher mucoadhesiveness when compared with non-thiolated particles. Cell-based assays revealed that thiolated particles are not cytotoxic and, importantly, increase TNF-α secretion in murine dendritic cells. Moreover, immunization assays revealed that thiolated PAA/Schizo particles induced a humoral response with a more balanced IgG2a/IgG1 ratio. Therefore, thiolated PAA/Schizo particles are deemed a promising delivery system whose evaluation in vaccine prototypes is guaranteed.

Synthesis and antiproliferative activity of new thiazole hybrids with [3.3.0]furofuranone or tetrahydrofuran scaffolds

New thiazole hybrids were synthesized and evaluated for their in vitro cytotoxicity against a panel of human malignant cell lines. The key steps in the synthesis of hybrids 3?7 involved the initial condensation of appropriate aldononitriles with cysteine ethyl ester hydrochloride, followed by subsequent treatment of resulting thiazolines with diazabicycloundecene to form the thiazole ring. Bioisosteres 8 and 14 have been prepared after the stereoselective addition of 2-(trimethylsilyl)thiazole to the hemiacetals obtained by periodate cleavage of terminal diol functionality in the suitably protected d-glucose derivatives. The obtained analogues showed various antiproliferative activities in the cultures of several tumour cell lines. Hybrid 6 was the most potent in HeLa cells, exhibiting more than 10 and 4 times stronger activity than both leads 1 and 2, respectively. The most active compound in Raji cells was hybrid 12, which was nearly 2-fold more potent than the clinical antitumour drug doxorubicin. All analogues were more potent in A549 cells with respect to lead 1, while compounds 6 and 7 were slightly more active than doxorubicin. Preliminary structure?activity relationship analysis revealed that the presence of a cinnamate group at the C-3 position in analogues of type 7 increases the activity of resulting molecular hybrids.

Construction of CdS-Tetrahymena thermophila hybrid system by efficient cadmium adsorption for dye removal under light irradiation

The water pollution caused by heavy metals and dyes emitted by industries has become a worldwide problem. These pollutants are difficult to be biodegraded. Even at low concentrations, they are toxic and at last threaten human health. Herein, while using Tetrahymena thermophila, a single-celled ciliate protozoa, to enrich and remove the heavy metal Cd2+ from water, CdS nanoparticle-Tetrahymena thermophila hybrid system (CdS-T. thermophila) for dye pollution remediation under light irradiation was developed. The conditions of Cd2+ enrichment and removal by T. thermophila, construction of efficient CdS-T. thermophila, and decolorization of Congo red using CdS-T. thermophila were investigated. In the presence of cysteine ethyl ester, the removal rate of Cd2+ by T. thermophila was 94% at low Cd2+ concentration of 1 mg L−1. The adsorption capacity of T. thermophila to Cd2+ reached 43 mg g−1 at Cd2+ concentration of 80 mg L−1. Using 0.1 g L−1 constructed CdS-T. thermophila, the decolorization rate of 50 mg L−1 Congo red solution reached 95% in 60 min under light irradiation. This study provides a new insight to effective removing Cd2+ from water by T. thermophila to construct the CdS-T. thermophila and using it to remediate dye pollution in the environment.

Design, synthesis, and biological evaluation of thiazole bioisosteres of goniofufurone through in vitro antiproliferative activity and in vivo toxicity

The synthesis of several new goniofufurone bioisosteres was achieved in which the phenyl residue was replaced by a thiazole ring. The key steps of the synthesis included the initial condensation of cyanohydrin benzoates with cysteine ethyl ester hydrochloride, followed by the subsequent reaction of resulting C-4′ epimeric thiazolines with DBU, to introduce 5-deoxy functionality and to elaborate the thiazole ring in one step. Synthesized compounds showed potent growth inhibitory effects against selected human tumour cell lines, especially bioisostere 4, which in the culture of MCF-7 cells displayed the highest activity (IC50 = 0.19 nM) of all compounds under evaluation. This molecule exhibited 64474-fold higher antiproliferative activity than lead 2 and was1053-fold more active than the commercial antitumour agent doxorubicin in the culture of MCF-7 cells. The structural features of the tested compounds responsible for their antiproliferative activity have been identified by preliminary SAR analysis. The toxicity of the most active compound 4 was assessed by an in vivo experiment in a zebrafish model (Danio rerio), whereupon it was found non-toxic at any of the tested concentrations up to 125 μM.

Oxidative Stress and Cognitive Alterations Induced by Cancer Chemotherapy Drugs: A Scoping Review.

Cognitive impairment is one of the most deleterious effects of chemotherapy treatment in cancer patients, and this problem sometimes remains even after chemotherapy ends. Common classes of chemotherapy-based regimens such as anthracyclines, taxanes, and platinum derivatives can induce both oxidative stress in the blood and in the brain, and these effects can be reproduced in neuronal and glia cell cultures. In rodent models, both the acute and repeated administration of doxorubicin or adriamycin (anthracyclines) or cisplatin impairs cognitive functions, as shown by their diminished performance in different learning and memory behavioural tasks. Administration of compounds with strong antioxidant effects such as N-acetylcysteine, gamma-glutamyl cysteine ethyl ester, polydatin, caffeic acid phenethyl ester, and 2-mercaptoethane sulfonate sodium (MESNA) counteract both oxidative stress and cognitive alterations induced by chemotherapeutic drugs. These antioxidant molecules provide the scientific basis to design clinical trials in patients with the aim of reducing the oxidative stress and cognitive alterations, among other probable central nervous system changes, elicited by chemotherapy in cancer patients. In particular, N-acetylcysteine and MESNA are currently used in clinical settings and are therefore attracting scientific attention.

Helical nanofibers of N-(perfluorooctanoyl)cysteine ethyl ester in coordination polymers of Ag.

We propose using the formation of coordination polymers of Ag+ to probe differences between the perfluorinated alkyl chain and the alkyl chain by deriving a thiol ligand, N-(perfluoroalkanoyl)cysteine. Rapid formation in EtOH of P-/M-helical nanofibrils of high thermostability was found for N-(perfluorooctanoyl)-l-/d-cysteine ethyl esters at the μM level upon mixing with Ag+, but not for the octanoyl counterpart. This difference was also observed in terms of circular dichroism-enantiomeric excess dependence.

Evaluation of modified hyaluronic acid in terms of rheology, enzymatic degradation and mucoadhesion

PurposeThis study aimed to investigate the properties of modified hyaluronic acid in terms of rheological properties, enzymatic degradation and mucoadhesiveness. MethodsHyaluronic acid (HA) was chemically modified with sulfhydryl ligand cysteine ethyl ester (C) in order to immobilize sulfhydryl groups on the polymeric backbone. MTT assay was performed to evaluate the safety of hyaluronic acid-cysteine ethyl ester (HAC). Rheological and enzymatic degradation studies were accomplished by preparing hydrogels of HA and HAC, respectively. HA served as control. Enzymes such as lysozyme, amylase and hyaluronidase were chosen to perform degradation studies. To study mucoadhesiveness, hydrogels of HA and HAC, respectively, were mixed with mucus and evaluated by rheology. ResultsMTT assay indicated no toxicity at all. The rheological assay showed 2.2-fold increase in gelling properties in case of HAC in comparison to HA. Furthermore, it could be shown that HAC was degraded by amylase to a lesser extent of 11.5-fold than HA. After 2 h, HA showed a higher degradation by lysozyme with 67.97% than HAC. Adhesion studies exhibited a 2.17-fold higher mucoadhesion of HAC with mucus compared to HA. ConclusionThese results will open the door for high efficient drug delivery systems based on hydrogels for mucosal application.

Novel adhesive hyaluronic acid based solid dosage form for pediatric application

The aim of this study was to develop a solid dosage form for pediatric application. For this purpose, hyaluronic acid was covalently linked with sulfhydryl groups of cysteine ethyl ester via amide bond formation mediated by carbodiimide. The obtained hyaluronic acid-cysteine ethyl ester was characterized in terms of degree of substitution, stability, mucoadhesive as well as mucoprotective and lubricative properties. Moreover, toxicity was evaluated on head and neck squamous cells as well as histology assay was performed via alcian blue staining. A novel solid dosage form was prepared and tested for its suitability for pediatric intraoral use. Obtained findings revealed sulfhydryl linked hyaluronic acid was safe to use as no irritation was detected on buccal mucosa. Stability assessment as disintegration and erosion of the matrix could be 12.0-fold and 5.23-fold in presence of hyaluronic acid-cysteine ethyl ester, respectively. The novel designed solid dosage forms provided 3.4-fold augmented lubrication in the intraoral cavity compared to respective hyaluronic acid. In conclusion, the delivery of drugs to children is still an unmet challenge to tackle. This novel excipient for smart dosage forms will pave the pathway for children's compliance to the next level of therapy.

Comparative mucoadhesive study of hyaluronic acid‐based conjugates on different mucosae

ABSTRACTThe incentive of this study was to provide a detailed mucoadhesive comparison on adhesive properties on diverse mucosal surfaces such as nasal, buccal, and vaginal mucosa, respectively. Mucoadhesive hyaluronic acid–cysteine ethyl ester (HA–SH) conjugate was synthesized by the anchorage of sulfhydryl groups (SH) on the polymeric backbone of HA via amide bond formation between the carboxylic acid moieties of hyaluronic acid and sulfhydryl groups of cysteine ethyl ester. Histology assay in terms of alcian blue staining was performed on mucosal tissue in order to evaluate the potential impact on viability. The proficiency of water uptake was studied in various simulated body fluid. Moreover, mucoadhesive assays based on rotating cylinder, total work of adhesion, and maximum detachment force were carried out on various mucosae. The findings revealed in presence of 2.7‐, 2.6‐, and 1.25‐fold improvement in swelling behavior in comparison to unmodified HA on nasal, buccal, and vaginal mucosa. Furthermore, mucoadhesive studies showed a 3.2‐, 2.6‐, 2.6‐fold more extended residence time on nasal, buccal, and vaginal in presence of HA–SH in comparison to unmodified HA, respectively. Taken together, the comprehensive mucoadhesive study serve as guidance in the development of mucoadhesive drug delivery systems for versatile application. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46071.

Synthesis, Antioxidative and Whitening Effects of Novel Cysteine Derivatives

Recently, development of biocompatibility functional cosmetic agents as antioxidant or whitening agent has increased. In this study, synthetic cysteine derivatives (DBLS‐21, ‐24, and ‐33) were developed containing syringic acid and cysteine moieties (l‐cysteine ethyl ester, N‐acetyl cysteine methyl ester, and N‐acetyl cysteine ethyl ester), and their antioxidative and whitening activities were evaluated. The cellular protective effect (τ50) of DBLS‐21 was 51.1 min at 50 μM on 1O2 ‐induced hemolysis of erythrocytes. This activity was slightly higher than that of α‐tocopherol (43.6 min) as a lipophilic antioxidant. In the melanogenesis inhibitory effect, DBLS‐21, ‐24, and ‐33 was 1.6‐, 1.8‐, and 2.5‐fold higher than arbutin, respectively. In particular, DBLS‐21 and ‐33 was 112.8‐ and 6.1‐fold higher than arbutin, respectively (293.4 μM) on tyrosinase inhibition activity (IC50 ). But DBLS‐24 had no tyrosinase inhibitory activity. These results suggest that cysteine derivatives possess potential for use as an antioxidant agent (DBLS‐21) and whitening agents (all derivatives) in cosmetics.

Neuroproteomic study of nitrated proteins in moderate traumatic brain injured rats treated with gamma glutamyl cysteine ethyl ester administration post injury: Insight into the role of glutathione elevation in nitrosative stress.

The aims of this study are to establish a time point to determine the most beneficial time to administer GCEE post incident to reduce oxidative damage and second, by using redox proteomics, to determine if GCEE can readily suppress 3-NT modification in TBI animals. By using a moderate traumatic brain injury model with Wistar rats, it is hypothesized that the role of 3-nitrotyrosine (3-NT) formation as an intermediate will predict the involvement of protein nitration/nitrosation and oxidative damage in the brain. In this experiment, the levels of protein carbonyls, 4-hydroxynonenal, and 3-nitrotyrosine were significantly elevated in TBI injured, saline treated rats compared with those who sustained an injury and were treated with 150 mg/kg of the glutathione mimetic, GCEE. Determining the existence of elevated 3-NT levels provides insight into the relationship between the protein nitration/nitrosation and the oxidative damage, which can determine the pathogenesis and progression of specific neurological diseases.

Synthesis and characterization of new M(II) carbonyl complexes (M = Fe or Ru) including an η1-N-maleimidato ligand. Reactivity studies with biological thiols

Herein we report the preparation and characterization of the iron and ruthenium organometallic maleimides (η5-Cp*)Fe(CO)2(η1-maleimidato) (Cp* = pentamethyl cyclopentadienyl) and (η5-Cp)Ru(CO)2(η1-maleimidato). The molecular structure of the ruthenium complex was confirmed by X-ray diffraction study. The reactivity of the metallocarbonyl maleimide derivatives toward biologically meaningful thiols, namely cysteine ethyl ester hydrochloride, glutathione (GSH) and human serum albumin (HSA) was investigated. To get better insight into the reaction mechanism, kinetic studies of the reaction with GSH and HSA were performed as well as quantum-chemical calculations and QTAIM analysis. We found out that the reactivity of the organometallic maleimides towards thiols depended on: 1) the metal present in the structure, 2) the nature of the capping aromatic ligand due to differences in electron donating capabilities and steric demands and 3) additional interactions like hydrogen bonding in (η5-Cp*)Fe(CO)2(η1-maleimidato) and carbonyl … carbonyl interactions in (η5-Cp)Ru(CO)2(η1-maleimidato).

Development of novel mucoadhesive hyaluronic acid derivate as lubricant for the treatment of dry eye syndrome.

Dry eye - a disease affecting between 4 and 34% of the population worldwide. Stressful conditions to ocular surface, contact lenses as well as systemic disease cause dry eye. Novel synthesized hyaluronic acid derivate was evaluated in terms of its potential as mucoadhesive and lubricant. Results & methodology: Hyaluronic acid was chemically modified with cysteine ethyl ester (hyaluronic acid-cysteine ethyl ester). Mucoadhesion, disintegration and water uptake capacity, moreover, safety as the hen's egg test for mucous membrane compatibility were evaluated. According to the results, hyaluronic acid-cysteine ethyl ester achieved 3.81-fold increased swelling capacity, 30.5-fold more improvement mucoadhesive properties and 9.72-fold higher stability of hyaluronic acid, which was achieved due to the chemical modification. Thus, the promising results underpin further exploitation of this versatile polysaccharide for treating dry eye syndrome.

A potential tailor-made hyaluronic acid buccal delivery system comprising rotigotine for Parkinson's disease?

Parkinson's disease (PD) affects over 10 million people around the world. Dysphagia is one of its main problems. Therefore, mucosal delivery is beneficial for patient compliance. This study aimed to synthesize mucoadhesive hyaluronic acid (HA) comprising rotigotine for the treatment of PD. HA - a biocompatible, naturally occurring polysaccharide - was chemically modified with the thiol-bearing ligand cysteine ethyl ester via amide bond formation (HAC). HAC was evaluated in terms of stability, cytotoxicity, permeation enhancement, controlled drug release and mucoadhesiveness. HAC showed 1.49-fold higher stability, 3.47-fold improved swelling capacity and 12.16-fold augmentation in mucoadhesion. Additionally, HAC exhibited 1.18-fold permeation enhancement over HA. Taking the findings into consideration, HAC represents a pillar of mucosal buccal delivery in the treatment of PD.

An oxidative coupling product of luteolin with cysteine ester and its enhanced inhibitory activity for xanthine oxidase.

Oxidative coupling reactions of several flavonoids with a cysteine ester (a radicalic and nucleophilic biochemical) were carried out and the abilities of the coupling products against xanthine oxidase (XO) were screened. One of the products, derived from luteolin, showed a notable inhibitory effect. A potent XO inhibitory compound was isolated from the complex mixture of the product of the coupling of luteolin and cysteine ethyl ester, and its structure was determined by NMR and MS analysis. The compound has a unique 1,4-thiazine ring unit on the luteolin B-ring and is inhibited XO 4.5 times more strongly than it did luteolin.

In Vitro and Ex Vivo Evaluation of Biomaterials' Distinctive Properties as a Result of Thiolation

Polysaccharide hyaluronic acid (HA) was chemically modified with cysteine ethyl ester (CYS). By immobilization of the thiol-bearing ligand on the polymeric backbone the thiolated bioconjugate HA-CYS was obtained. METHODOLOGY & RESULTS: Mucoadhesion, permeation enhancement effect and stability was tested. Furthermore mechanical, physicochemical properties as well as mucoadhesive strength, swelling index and residence time on the mucosa were investigated. The developed thiolated bioconjugate displayed 1.5-fold improved mucoadhesiveness on buccal mucosa as well as an enhanced permeation behavior and 2.5-fold higher polymer stability. The near neutral pH and 2.49±0.49% cytotoxicity over 12-h studies indicated their non-irritability and biocompatible nature with biological tissues. Further, the model drug sulforhodamine 101 was incorporated to determine its drug release profiles, which revealed a 2.8-fold controlled release of HA-CYS in comparison to unmodified HA. Thus, the promising results encourage further investigations and exploitation of this versatile polysaccharide.

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.

A Facile, Inexpensive and Scalable Route to Thiol-Protected α-Methyl Cysteine

A facile, scalable synthesis of α-methyl cysteine with three alternate thiol protecting groups (trityl, allyl and tert-butyl) is described. The thiol-protected amino acids are obtained in six steps from l -cysteine ethyl ester and are ideally suited for a range of natural product and solid-phase peptide synthesis applications.

Metallocarbonyl complexes of bromo‐ and dibromomaleimide: synthesis and biochemical application

Bromomaleimides react with cysteine residues to form thiomaleimides that can be further cleaved with TCEP (tris(2‐carboxyethyl)phosphine) to regenerate the cysteine derivatives. Herein we report the preparation of new organometallic Fe complexes containing monobromo and dibromo maleimide ligands. Both of these complexes were characterised by X‐ray diffraction. Organometallic bromomaleimide derivatives were reacted with the thiol‐containing biomolecules: cysteine ethyl ester hydrochloride, glutathione and papain. These cysteine‐containing molecules underwent a substitution reaction with metallocarbonyl bromo‐ or dibromo maleimide complexes, followed by an addition reaction to the thio‐maleimide double bond if thiol was added in excess. The metallocarbonyl mono‐bromomaleimide complex was shown to inhibit the peptidase activity of the enzyme papain. The resulting papain–maleimide product could be cleaved by addition of TCEP to regenerate the catalytically active enzyme. Copyright © 2012 John Wiley & Sons, Ltd.