Study on determination of 2-thioxothiazolidine-4-carboxylic Acid in urine by high performance liquid chromatography / 中华劳动卫生职业病杂志

Objective: To establish a high performance liquid chromatography method for the determination of 2-thioxothiazolidine-4-carboxylic acid (TTCA) in urine. Methods: After acidification with hydrochloric acid, TTCA in urine was first extracted by ethyl acetate with excessive sodium chloride, then gradient separated by a symmetry C18 column and then detected by a diode array detector. The quantification was based on a working curve of external standard method. Results: The linear relationship of TTCA in urine was good in the range of 0.03-10.00 mg/L, and the correlation coefficient was 0.9999. The detection limit and minimum quantitative concentration of TTCA in urine were 0.008 mg/L and 0.027 mg/L. The intra-assay precision of the method was 0.9%-1.4%, the inter-assay precision was 1.3%-3.5%, and the average recovery was 85.0%-92.7% while the concentrations of TTCA in urine was 0.8, 2.0 and 8.0 mg/L, respectively (n=6) . Conclusion: The gradient elution high performance liquid chromatography method has simple operation and high sensitivity, and it is suitable for the determination of TTCA on a low level in urine for occupational workers exposure to carbon disulfide.

Determination of creatinine and 2-thiothiazolidine-4-carboxylic acid in urine by ultra high performance liquid chromatography tandem mass spectrometry / 中华劳动卫生职业病杂志

Objective: To establish an ultrahigh performance liquid chromatography tandem mass spectrometry method for the determination of creatinine (Cre) and 2-thiothiazolidine-4-carboxylic acid (TTCA) in urine. Methods: In October 2020, the end-of-shift urine samples of the monitored subjects were taken, and the filtrate was prepared by centrifugation. After separated by ultra high performance liquid chromatography C18 column, acetonitrile and 0.2% acetic acid aqueous solution were used as mobile phases for gradient elution, the three quadrupole tandem mass spectrometry adopted an electrospray ion source (ESI) , the ion source temperature was 500 ℃ , and the air curtain gas flow rate was 31.4 L/min, qualitative and quantitative analysis of Cre and TTCA were carried out under the multiple reaction monitoring mode. Results: The linear range of Cre was 1.0-1 000.0 μg/L, the linear equation was y=947.3x-1605.6, and the correlation coefficient was 0.9994. The detection limit and the limit of quantitation were 0.3, 1.0 μg/L. When the addition concentrations were 50.0, 150.0 and 450.0 μg/L, the recovery rates were 92.8%-94.6% , the intra assay precisions were 3.6%-5.7% , and the inter assay precisions were 3.4%-5.4%. The linear range of TTCA was 0.1-200.0 μg/L, the linear equation was y=1164.7x-2243.9, and the correlation coefficient was 0.9991. The detection limit and the limit of quantitation were 0.03, 0.1 μg/L. When the addition concentrations were 10.0, 40.0 and 160.0 μg/L, the recovery rates were 90.8%-93.6%, the intra assay precisions were 4.6%-7.4%, and the inter assay precisions were 4.4%-6.9%. Conclusion: The sample pretreatment process of the ultra high performance liquid chromatography tandem mass spectrometry method for the determination of Cre and TTCA in urine is simple, and the continuous determination of Cre and TTCA in urine can be realized only by switching mass spectrometry parameters under the same chromatographic conditions, which is accurate and efficient, and each performance index of the method meets the determination requirements.

Synthesis of New Thiazole Derivatives Bearing Thiazolidin-4(5H)-One Structure and Evaluation of Their Antimicrobial Activity

The first report about antimicrobial resistance was published in the 1940s. And today, the antimicrobial resistance has become a worldwide problem. Because of this problem, there is a need to develop new drugs. That's why we synthesized some novel thiazolidine-4-one derivatives and evaluated their antimicrobial activity. The final compounds were obtained by reacting 2-[(4,5-diphenylthiazol-2-yl)imino]thiazolidin-4-one with some aryl aldehydes. The synthesized compounds were investigated for their antimicrobial activity against four Candida species, five gram-negative and four gram-positive bacterial species. The lead compounds (4a- h) were obtained with a yield of at least 70%. All compounds showed antimicrobial activity. Compound 4f (MIC: 31.25 µg/ml) exhibited more efficacy than the other compounds against C. glabrata (ATCC 24433). Compound 4b (MIC: 62.5 µg/ml) was the most active compound against all bacterial species, particularly K. pneumoniae (NCTC 9633). Whereas, compound 4c (MIC: <31.25 µg/ml) was observed as the most active compound against E. coli (ATCC 25922). In general, all compounds (4a-4h) showed antimicrobial activity against all fungi and bacterial species. Compounds 4b (2,6-dichlorobenzylidene), 4c (2,6-dihydroxybenzylidene), 4f (1H-pyrrol-2- yl)methylene), 4g (4-triflouromethylbenzylidene) and 4h (2,3,4-trimethoxybenzylidene) were determined as the most active compounds

Interventional effect of epalrestat on renal interstitial fibrosis in unilateral ureteral obstruction rats and its mechanism / 中国应用生理学杂志

OBJECTIVE@#To observe the protective effects of epalrestat (EPS) on interstitial fibrosis in unilateral ureteral obstruction (UUO) rats and its mechanism.@*METHODS@#Rats were randomly divided into four groups: sham group, UUO group, UUO + epalrestat (50 or 100 mg/kg), 8 rats in each group.Rats in UUO and UUO + epalrestat group were obstructed left ureter.In the sham group, rats had their left ureters exposed and manipulated without ligation.Animals for epalrestat treatment received daily drug via gavage for 3 weeks, the rats of sham and UUO groups received equal amount of sodium carboxymethyl cellulose with the same regimen.Renal tissues pathological changes and collagen deposition were observed by HE and Masson's staining.The aldose reductase(AR) expression in renal tissues was measured by immunohistochemisty.The expression levels of collagen I, collagen III, alpha-smooth muscle actin (α-SMA), fibroblast-specific protein1 (FSP-1), fibronectin (FN), epithelial cadherin (E-cadherin), transforming growth factor-β1 (TGF-β1) and AR from kidney tissues were measured by real-time RT-PCR or Western blot.@*RESULTS@#Compared with the sham group, the renal tissues of the UUO group showed significant fibrosis, including renal tubular epithelial cell atrophy and vacuolated degeneration, collagen deposition, fibroblasts and myofibroblasts proliferation and inflammatory cell infiltration, and concomitantly with the expressions of collagen I, collagen III, TGF-β1, AR, α-SMA, FSP-1 and FN were remarkably up-regulated, but E-cadherin was significantly reduced in UUO group.Compared with the UUO group, after 3 weeks epalrestat administration, the level of renal interstitial fibrosis was obviously ameliorated and the expressions of collagen I, collagen III, TGF-β1, AR, α-SMA, FSP-1 and FN were remarkably down-regulated, but E-cadherin was significantly increased in rats of epalrestat groups.@*CONCLUSION@#These results suggest that epalrestat attenuates renal interstitial fibrosis possibly through inhibition of EMT via inhibiting TGF-β1 and AR expression.

Clinical effect of pidotimod oral liquid as adjuvant therapy for infectious mononucleosis / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the clinical effect of pidotimod oral liquid as adjuvant therapy for infectious mononucleosis and its effect on T lymphocyte subsets.</p><p><b>METHODS</b>A total of 76 children with infectious mononucleosis, who were admitted to the hospital between July 2016 and June 2017, were enrolled and randomly divided into two groups: conventional treatment and pidotimod treatment (n=38 each). The children in the conventional treatment group were given antiviral therapy with ganciclovir for injection and symptomatic treatment. Those in the pidotimod treatment group were given pidotimod oral liquid in addition to the treatment in the conventional treatment group. The course of treatment was two weeks for both groups. The two groups were compared in terms of the recovery of clinical indices and the changes in peripheral blood T lymphocyte subsets.</p><p><b>RESULTS</b>Compared with the conventional treatment group, the pidotimod treatment group had significantly shorter fever clearance time, time to the disappearance of isthmopyra, time to the relief of lymph node enlargement, time to the relief of hepatosplenomegaly, and length of hospital stay (P<0.05). After treatment, the pidotimod treatment group had significant reductions in the percentages of CD3 and CD8 T cells and had significantly lower percentages of CD3 and CD8 T cells than the conventional treatment group (P<0.001). The pidotimod treatment group had significant increases in the percentage of CD4 T cells and CD4/CD8 ratio after treatment, which was significantly higher than those in the conventional treatment group (P<0.001). The conventional treatment group had no significant changes in T lymphocyte subsets after treatment (P>0.05).</p><p><b>CONCLUSIONS</b>Pidotimod oral liquid has a good clinical effect as the adjuvant therapy for infectious mononucleosis and can improve cellular immune function, so it holds promise for clinical application.</p>

Yap1 plays a protective role in suppressing free fatty acid-induced apoptosis and promoting beta-cell survival

Mammalian pancreatic β-cells play a pivotal role in development and glucose homeostasis through the production and secretion of insulin. Functional failure or decrease in β-cell number leads to type 2 diabetes (T2D). Despite the physiological importance of β-cells, the viability of β-cells is often challenged mainly due to its poor ability to adapt to their changing microenvironment. One of the factors that negatively affect β-cell viability is high concentration of free fatty acids (FFAs) such as palmitate. In this work, we demonstrated that Yes-associated protein (Yap1) is activated when β-cells are treated with palmitate. Our loss- and gain-of-function analyses using rodent insulinoma cell lines revealed that Yap1 suppresses palmitate-induced apoptosis in β-cells without regulating their proliferation. We also found that upon palmitate treatment, re-arrangement of F-actin mediates Yap1 activation. Palmitate treatment increases expression of one of the Yap1 target genes, connective tissue growth factor (CTGF). Our gain-of-function analysis with CTGF suggests CTGF may be the downstream factor of Yap1 in the protective mechanism against FFA-induced apoptosis.

Impact of the CFTR chloride channel on the cytoskeleton of mouse Sertoli cells / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the impact of the chloride channel dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) on the cytoskeleton of Sertoli cells in the mouse.</p><p><b>METHODS</b>TM4 Sertoli cells were cultured and treated with CFTR(inh)-172 at the concentrations of 1, 5, 10 and 20 μmol/L for 48 hours. Then the cytotoxicity of CFT(inh)-172 was assessed by CCK-8 assay, the expressions of F-actin and Ac-tub in the TM4 Sertoli cells detected by immunofluorescence assay, and those of N-cadherin, vimentin and vinculin determined by qPCR.</p><p><b>RESULTS</b>CFTR(inh)-172 produced cytotoxicity to the TM4 Sertoli cells at the concentration of 20 μmol/L. The expressions of F-actin and Ac-tub were decreased gradually in the TM4 Sertoli cells with the prolonging of treatment time and increasing concentration of CFTR(inh)-172 (P < 0.05). The results of qPCR showed that different concentrations of CFTR(inh)-172 worked no significant influence on the mRNA expressions of N-cadherin, vimentin and vinculin in the Sertoli cells.</p><p><b>CONCLUSION</b>The CFTR chloride channel plays an important role in maintaining the normal cytoskeleton of Sertoli cells. The reduced function and expression of the CFTR chloride channel may affect the function of Sertoli cells and consequently spermatogenesis of the testis.</p>

Synthesis, DNA cleavage and antimicrobial activity of 4-thiazolidinones-benzothiazole conjugates.

Antimicrobial screening of several novel 4-thiazolidinones with benzothiazole moiety has been performed. These compounds were evaluated for antimicrobial activity against a panel of bacterial and fungal strains. The strains were treated with these benzothiazole derivatives at varying concentrations, and MIC’s were calculated. Structures of these compounds have been determined by spectroscopic studies viz., FT-IR, 1H NMR, 13C NMR and elemental analysis. Significant antimicrobial activity was observed for some members of the series, and compounds viz. 3-(4-(benzo[d]thiazol-2-yl) phenyl)-2-(4-methoxyphenyl)thiazolidin-4-one and 3-(4-(benzo[d]thiazol-2-yl)phenyl)-2-(4-hydroxy phenyl)thiazolidin-4-one were found to be the most active against E.coli and C.albicans with MIC values in the range of 15.6–125 μg/ml. Preliminary study of the structure–activity relationship revealed that electron donating groups associated with thiazolidine bearing benzothiazole rings had a great effect on the antimicrobial activity of these compounds and contributes positively for the action. DNA cleavage experiments gave valuable hints with supporting evidence for describing the mechanism of action and hence showed a good correlation between their calculated MIC’s and its lethality.

A quantitative structure-activity relationship (QSAR) study on a few series of potent, highly selective inhibitors of nitric oxide synthase.

QSAR study was performed on a series of 1,2-dihydro-4-quinazolinamines, 4,5-dialkylsubstituted-2-imino-1,3-thiazolidine derivatives and 4,5-disubstituted-1,3-oxazolidin-2-imine derivatives studied by Tinker et al. [J Med Chem (2003), 46, 913-916], Ueda et al. [Bioorg Med Chem (2004) 12, 4101-4116] and Ueda et al. [Bioorg Med Chem Lett (2004) 14, 313-316], respectively, as potent, highly selective inhibitors of inducible nitric oxide synthase (iNOS). The iNOS inhibition activity of the whole series of compounds was analyzed in relation to the physicochemical and molecular properties of the compounds. The QSAR analysis revealed that the inhibition potency of the compounds was controlled by a topological parameter 1v (Kier’s first order valence molecular connectivity index), density (D), surface tension (St) and length (steric parameter) of a substituent. This suggested that the drug-receptor interaction predominantly involved the dispersion interaction, but the bulky molecule would face steric problem because of which the molecule may not completely fit in active sites of the receptor and thus may not have the optimum interaction.

Synthesis and biological evaluation of some novel furan derivatives

The present work involved cyclization of Schiff bases to azetidine-2-one and thiazolidine 4-one derivatives. The schiff bases [IIIa-j] were obtained upon reaction between electrophillic carbon atom of furfuraldehyde and nucleophillic nitrogen atom of amines. Azetidine-2-one derivatives [IVa-j] were obtained by reaction between imines and monochloro acetyl chloride in the presence of triethyl amine and 1, 4 dioxan. On the other hand, preparations of thiazolidine-4-ones [Va-j] were preceded by nucleophilic attack of sulphur of thioglycolic acid on imine carbon followed by intramolecular cyclization in the presence of SnCl[2]. The structures of the compounds were confirmed by spectral and elemental analysis. The biological evaluation of the compounds like anti-microbial, antioxidant, analgesic, CNS depressant and anti-diabetic activity were determined. From the pharmacological investigation it was found that out of all the compounds IVa, IVb, IVe, IVf, IVh,Va, Vb, Ve, Vf, Vh had shown more potent activity

The activation effect of nobiletin on cystic fibrosis transmembrane conductance regulator chloride channel / 药学学报

Aim of the present study is to investigate activation effect of nobiletin on cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel activity. CFTR-mediated iodide influx assay and patch-clamp tests were done on FRT cells stably co-transfected with human CFTR and EYFP/H148Q. Nobiletin potently activated CFTR chloride channel activity in a dose- and time-dependent manner. The CFTR blocker CFTR(inh)-172 could completely reverse the effect. Preliminary mechanism study indicated that nobiletin activated CFTR chloride channel through a direct binding way. In addition, ex vivo tests done on mice trachea showed that nobiletin time-dependently stimulated submucosal gland fluid secretion. Nobiletin may be a therapeutic lead compound in treating CFTR-related diseases including disseminated bronchiectasis.

Protective effect of epalrestat against high glucose-induced endothelial cell injuries / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the protective effect of epalrestat against endothelial cell injuries induced by high glucose.</p><p><b>METHODS</b>Human umbilical vein endothelial cells were pretreated with epalrestat (0.1 µmol/L) for 30 min followed by exposure to high glucose for 8 h. NO concentration in the cell culture supernatant was assayed using chemiluminescence method following the exposure. Real-time PCR and Western blotting were used to detect eNOS mRNA and protein expression levels and the protein expressions of AR gene (the target gene of epalrestat) and NOX4 (the upstream gene of NO).</p><p><b>RESULTS</b>Compared with mannitol treatment, an 8-h exposure to high glucose caused significantly decreased NO levels and eNOS mRNA and protein expression in the vascular endothelial cells (P<0.05). Pretreatment with epalrestat prior to high glucose exposure resulted in elevated eNOS mRNA and protein expression levels and NO up-regulation in the cell culture as compared with the glucose exposure alone group (P<0.05), causing also decreased expression of AR and NOX4 in the cells.</p><p><b>CONCLUSIONS</b>High glucose can induce endothelial cell damage characterized by a lowered level of NO secretion. Epalrestat can protect the endothelial cells against high glucose-induced injury by inhibiting the expression of AR and NOX4.</p>

The optimization of 2-thiothiazolidine-4-carboxylic acid back extraction in urine and determination by HPLC / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>Establishment of determination method of 2-thiothiazolidine-4-carboxylic acid (TTCA) in urine with HPLC.</p><p><b>METHODS</b>A volume of 0.5 ml hydrochloric acid (2 mol/L) and 0.5 ml pure water was added into 1 ml urine, and then extracted by 4 ml of diethyl ether by shaking for 2 min. Remove the water phase in a tube with plug and extract again, mix the two extraction diethyl ether together, take 4 ml by adding 2 ml borax-monopotassium phosphate buffer and shaking for 2 min to extract, then take the water phase to detect. A C(18) column and UV detector were used for separating and detecting. The wavelength was 273 nm, the flow rate was 1.0 ml/min, and the injection volume was 20 µl.</p><p><b>RESULTS</b>TTCA has a good linearity (r = 0.9995) over the concentration of1 1 ∼ 10 µg and the minimum detectable concentration of TTCA in urine was 0.1 µg/ml. The within-day precision (RSD) were 8.4%, 3.0% and 1.7%, the between-day precision (RSD) were 11%, 3.8%, 1.9%, respectively. The extraction recovery were between 80% ∼ 102%.</p><p><b>CONCLUSION</b>The method was accurate and sensitive to detect TTCA in urine.</p>

The rervising of biological exposure index for carbon disulfide exposuring / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the biological exposure index of carbon disulfide in China.</p><p><b>METHODS</b>High-performance liquid chromatography (HPLC) was used to detect the levels of 2-thiothiazolidine-4-carboxylic acid (TTCA) in the urine of the workers after working shift end, Gas chromatography was used to detect the concentrations of the carbon disulfide in the workplace air. The relationship between the urine TTCA levels and the concentrations of the carbon disulfide was analyzed, the biological exposure index and judgement result from PC-TWA were compared.</p><p><b>RESULTS</b>The levels of TTCA in urine of workers occupationally exposed to carbon disulfide were closely and positively related with the concentrations of the carbon disulfide in the workplace air. The regression equation was Y = 0.265X - 0.165, The biological exposure index of carbon disulfide were calculated by regression equation according to occupational exposure limits of carbon disulfide in China.</p><p><b>CONCLUSION</b>The biological exposure index of CS(2) in China might be revised for 1.2 mg/g Cr.</p>

A clinical study on leucogen tablets therapy efficacy during PEG-alpha interferon and alpha-interferon in chronic hepatitis B / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To discuss the efficacy of Leucogen tablets treatment lessen the hematological reaction and raise the efficacy therapy of interferon in chronic hepatitis B treated with PEG-alpha interferon and alpha interferon.</p><p><b>METHODS</b>A total of 395 patients with HBeAg-positive chronic hepatitis B (CHB) inpatients from January 2002 to February 2011. Group: All the patients were assigned to A or B according as during the treatment added Leucogen tablets or not.</p><p><b>RESULTS</b>(1) All of 35.9% patients had neutrophil counts decrease under 1 x 10(9)/L, A group had 29.6%, B had 42.8% patients, P = 0.01; neutrophil counts < or = 0.75 x 10(9)/L A group had 12.6% ,B group had 26.4%, P = 0.02; neutrophil counts < or = 0. 5 x 10(9)/L A group had 4.8%, B group had 16.4%, P = 0.04. (2) A group had 8.2% patients interferon-alpha dose decreased, all the patient finished the period of therapy. B group had 23.3% patients interferon-alpha dose decreased, 2.1% of patients had paused. A group had 40.3% of patients interferon-alpha beyond conventional dose, B group had only 5.2%. (3) All of 9.8% patients had hematoblast decrease under 100 x 10(9)/L, A group had 8.7%, B had 11.1% patients; hematoblast < or = 80 x 10(9)/L A group had 5.3%, B group had 7.9%; hematoblast < or = 50 x 10(9)/L A group had 1.0%, B group had 2.6%. A group had the trend of reducing hematoblast decrease. (4) At the end of therapy A group had 67.4% patients HBVDNA < 100IU/ml, 54.3% e antigen negative, 40.7% e antigen conversed; B group had 53.9%, 41.2%, 26.9%, P was respectively 0.02, 0.01, 0.01.</p><p><b>CONCLUSION</b>Leucogen tablets treatment and prevention interferon-alpha-related neutrophil counts hematological reaction in CHB treated with alpha-interferon, and had the trend of reducing interferon-alpha-related hematoblast decrease, farther improved the efficacy of alpha-interferon treatment CHB.</p>

Research progress in aldose reductase / 中南大学学报(医学版)

Aldose reductase is a member of aldehyde-keto reductase superfamily widely existing in the kidney, adrenal gland, lens, retina, nerve, heart, placenta, brain, skeletal muscle, testis, blood vessels, lung, liver, et al. It is a reduced nicotinamide-adenine dinucleotide phosphate (NADPH)-dependent enzyme catalyzing the reduction of various aldehydes and ketones to the corresponding alcohol. It is involved in many oxidative stress diseases, cell signal transduction and cell proliferation process as well as diabetes complications. In recent years, some progress has been made in research of the activity and gene regulation of aldose reductase and the relation with many common diseases.

Synthesis and evaluation of some new substituted 2-Aryl-3-[4'-[1"-[3"'-chlorophenyl]- phthalazine]]-4-thiazolidione as potential antifungal and insecticide

2-[3-chlorophenyl]-benzamide was condensed with hydrazine hydrochloride in presence of 10% NaOH to yield 1-[3-chlorophenyl]-4-amino pththalazine [I]. Seven new Schiff bases [II a-g] have been synthesized by the interaction of I with different aromatic aldehyde in dioxane. In final step II was condensed with thioglycolic acid in the presence of acetic acid to yield substituted-2-aryl-3-[4'[1"-3"'-chlorophenyl] phthalazine]]-4-thiazolidione. The synthesized compounds have been characterized by elemental analysis, IR, PMR and Mass spectral analysis and screened for antifungal and insecticidal activity

protective effects of N-acetl-cysteine, oxo-thiazolidine-carboxylate, acetaminophen and their combinations against sulfur mustard cytotoxicity on human skin fibroblast cell line [HF2FF]

Using human skin-fibroblast cell line HF2FF, the efficacy of some drugs was evaluated against sulfur mustard [SM] cytotoxicity. The drugs were the sulfhydryl containing molecule including Nacetylcysteine [NAC], 2-oxo-thiazolidine-4-carboxylate [OTC] and acetaminophen as glutathione [GSH] stimulator pathway. The protective effects of NAC [0.1 mM], OTC [1.8 mM], and acetaminophen [25 mM] alone or in combination with each other were evaluated on SM [180 micro M]-induced cytotoxicity. NAC and OTC were applied with SM simultaneously and acetaminophen 30 min before SM exposure, incubated for 1 h and then were rinsed and incubated with fresh medium. The efficacy was evaluated by determination of cells viability, intracellular GSH level and catalase activity 1 and 24 h post SM exposure or co-treatments. The cells viability was decreased 21.8% and 55.2%, respectively for 1 and 24 h post SM [1 h exposure] incubation. So, the 1-h SM exposure and 24-h treatment incubation were selected for evaluation. While, NAC alone treatment increased the cells viability [25%], GSH level [320%] and catalase activity [18%], the most effective combination was NAC plus OTC and acetaminophen which increased more significantly the cells viability [about 40%], GSH level [470%] and catalase activity [100%]. The most effective combination was NAC [0.1 mM] plus OTC [1.8 mM] and acetaminophen [25 mM] which should be used before or concomitant with SM exposure. These drugs may reduce SM toxicity possibly by increment of GSH level and catalase activity. This efficacy needs to be confirmed by in vivo study

Inhibition effect of epalrestat on rat lens osmotic expansion / 药学学报

Epalrestat is the unique aldose reductase inhibitor on the market, which was mainly used for the diabetic neuropathy. Lenses osmotic expansion could be induced by galactose to mimic the pathological process of diabetic cataract in vitro. In present study, we mainly investigated whether epalrestat possesses inhibitory effect on the lens osmotic expansion. The results indicated that epalrestat could not only markedly inhibit rat lens osmotic expansion in vitro, but also significantly reduced the high expression of the osmotic expansion-related genes such as AR and AQP1 in mRNA and protein levels. The findings may provide an important reference to epalrestat in the clinical application for the treatment of diabetic cataract.

Synthesis of 1-benzyl and 1-benzoyl -3-indole derivatives with expected antimicrobial activity

Schiff's bases 2[a,b] were prepared via the reaction of 1-substituted indole-3-carboxaldehydes 1[a,b] with p-methoxyaniline in glacial acetic acid. Electrophilic addition of hydrogen bromide to compounds 2 [a,b] gave 3[a,b], which were reacted with hydrazine hydrate to yield the hydrazino derivatives 4[a,b]. Cyclization of the latter compounds using carbon disulphide and 1,2-dibromoethane gave triazolidine and triazine derivatives 5[a,b] and 6[a,b], respectively. Also, reaction of compounds 2[a,b] with thiosalicylic acid and thioglycolic acid led to the formation of benzothiazinone and thiazolidinone derivatives 7[a,b] and 8[a,b], respectively. Condensation of 8[a,b] with various arylaldehydes gave 9[a,b]-11[a,b] which condensed with hydrazine hydrate and cyclized to afford the fused pyrazolo [3,4-d] thiazole derivatives 12[a,b]-14[a,b]. Moreover, reaction of 8[a,b] with paraformal-dehyde and secondary amines, namely morpholine and N-methyl piperazine gave the corresponding Mannich's products 15[a,b] and 16[a,b], respectively. The newly synthesized compounds were investigated for their antimicrobial activity against Gram-negative and Gram-positive bacteria and Fungi using Naldixic acid, Itraconazole and Nystatin as reference drugs. Some of the synthesized compounds showed high and moderate activity against various tested bacterial and fungal strains. MIC of the highly biological active compounds was also investigated