Methamphetamine (METH), a highly addictive drug used worldwide, induces oxidative stress in various animal organs. Recent animal studies indicate that methamphetamine also induces oxidative stress in the retina, which...Methamphetamine (METH), a highly addictive drug used worldwide, induces oxidative stress in various animal organs. Recent animal studies indicate that methamphetamine also induces oxidative stress in the retina, which is an embryonic extension of the forebrain. The aim of this study, therefore, was to evaluate the protecttive effects of N-acetylcysteine amide (NACA) against oxidative stress induced by METH in retinal pigment epithelium (RPE) cells. Our studies showed that NACA protected against METH-induced oxidative stress in retinal pigment epithelial cells. Although METH significantly decreased glutathione (GSH) levels and increased reactive oxygen species (ROS) and malondialdehyde (MDA) levels, these returned to control levels with NACA treatment. Overall observations indicated that NACA protected RPE cells against oxidative cell damage and death by inhibiting lipid peroxidation, scavenging ROS, increasing levels of intracellular GSH, and maintaining the antioxidant enzyme activity and the integrity of the bloodretinal barrier (BRB). The effectiveness of NACA should be further evaluated to determine its potential for the treatment of numerous retinal diseases caused by oxidative stress.展开更多
Glucocorticoids (GCs) are one of the most widely used immunosuppressive and anti-inflammatory agents. However, their long term and systemic use is associated with adverse drug reactions including posterior subcapsular...Glucocorticoids (GCs) are one of the most widely used immunosuppressive and anti-inflammatory agents. However, their long term and systemic use is associated with adverse drug reactions including posterior subcapsular cataracts as one of its ocular complications. Balanced redox state is crucial for maintenance of lens transparency, and a high content of glutathione (GSH) in the lens is believed to play a key role in doing so. Depletion of GSH is implicated in the etiopathogenesis of dexamethasone-induced cataracts and, therefore, the present study was sought to evaluate the efficacy of a novel thiol antioxidant, N-acetylcysteine amide (NACA), in preventing dexamethasone-induced cataractogenesis. Cataract formation was induced by incubation of rat lenses with 5 μM dexamethasone. To assess whether NACA had a significant impact on dexamethasone-induced cataracts, the rat lenses were divided into four groups: 1) control group (Dulbecco’s Modified Eagle Medium (DMEM), 2) dexamethasone group (DMEM with 5 μM dexamethasone), 3) NACA-only group (50 μM NACA solution), and 4) NACA pretreatment group (50 μM NACA for 6 hours followed by 5 μM dexamethasone only for 18 hours). Lenses were cultured for 7 days at 37°C under 5% CO2. Lenses were evaluated daily using a dissecting microscope and photographed and graded for the development of opacity. The rat lenses in both the control and the NACA-only groups were clear, whereas all lenses within the dexamethasone-only group developed well-defined cataracts. Overall observations indicated that NACA inhibits cataract formation by limiting lipid peroxidation and increasing the ratio of GSH/GSSG in lens. Therefore, NACA can be developed into a potential adjunctive therapeutic option for patients undergoing therapy with GCs to inhibit glucocorticoid-induced cataracts.展开更多
The title compound 3-bromo-5-（4-chlorophenyl）-4-cyanopyrrole-N,N-dimethyl-2-amide（3） was synthesized with 4-bromo-2-（4-chlorophenyl）-5-（trifluoromethyl）-1H-pyrrole-3-carbonitrile（1） and N,N-dimethylformamide...The title compound 3-bromo-5-（4-chlorophenyl）-4-cyanopyrrole-N,N-dimethyl-2-amide（3） was synthesized with 4-bromo-2-（4-chlorophenyl）-5-（trifluoromethyl）-1H-pyrrole-3-carbonitrile（1） and N,N-dimethylformamide（2） by the α-C acylation reaction catalyzed by potassium t-butoxide, and characterized by IR, 1H-NMR and X-ray single-crystal diffraction. It crystallizes in monoclinic, space group P2（1/n）with a = 12.789（2）, b = 13.783（2）, c = 17.980（3） °, β = 109.230（3）°, V = 2992.5 A3, Mr = 352.62, Dc = 1.565 mg/m3, Z = 8, m = 2.924 mm-1, F（000） = 1408, the final R = 0.0424 and w R = 0.0973 for 3518 observed reflections with I 〉 2σ（I）. A total of 23559 reflections were collected, of which 6242 were independent（Rint = 0.0566）. The insecticidal, herbicidal and antibacterial activities of compound 3 were determined, and the experimental results showed that the mortality of 3 at the concentration of 100 ppm on the Fipronil against Linnaeus was 76.6%, the growth inhibition rate of 3 against Cynodon Dactylon under the condition of 100 ppm was 35.8% and the inhibitory activity of 3 at the concentration of 25 ppm against Fusarium graminearum reached 50.9%. Hence, the title compound has the value of further research and application prospect.展开更多
A lab-incubation experiment was conducted to investigate the effects of different forms of nitrogen application （ammonium, NH4＋-N; nitrate, NO3--N; and amide-N, NH2-N） and different concentrations （40, 200 and 800...A lab-incubation experiment was conducted to investigate the effects of different forms of nitrogen application （ammonium, NH4＋-N; nitrate, NO3--N; and amide-N, NH2-N） and different concentrations （40, 200 and 800 mg L-1） on N2O emission from the fluvo-aquic soil subjected to a freezing-thawing cycling. N2O emission sharply decreased at the start of soil freezing, and then showed a smooth line with soil freezing. In subject to soil thawing, N2O emission increased and reached a peak at the initial thawing stage. The average N2O emissions with addition of NH4＋-N, NO3 -N and NH2-N are 119.01, 611.61 and 148. 22 ug m-2 h-1, respectively, at the concentration of 40 mg L-1; 205.28, 1 084.40 and 106.13 ug m2 h-1 at the concentration of 200 mg L-1; and 693.95, 1 820.02 and 49.74 ug m-2 h4 at the concentration of 800 mg L-1. The control is only 100.35 ug m-2 h-1. N2O emissions with addition of NH4＋-N and NO3--N increased with increasing concentration, by ranging from 17.49 to 425.67% for NH4＋-N, and from 563.38 to 1458.6% for NO3--N compared with control. There was a timelag for N2O emission to reach a steady state with an increase of concentration. In contrast, by adding NH2-N to soil, N2O emission decreased with increasing concentration. In sum, NH4＋-N or NO3--N fertilizer incorporated in soil enhanced the cumulative N2O emission from the fluvo-aquic soil relative to amide-N. This study suggested that ammonium and nitrate concentration in overwintering water should be less than 200 and 40 mg L-1 in order to reduce N2O emissions from soil, regardless of amide-N.展开更多
Amides are among the fundamental chemicals in organic chemistry.Compared to other carbonyl functional groups,the transformation of amide is relatively difficult and remains a challenge.The traditional deconstruction t...Amides are among the fundamental chemicals in organic chemistry.Compared to other carbonyl functional groups,the transformation of amide is relatively difficult and remains a challenge.The traditional deconstruction transformations of amides to other functional products are usually limited to twisted or electronically activated amides.Herein,we describe a direct nitrogenation approach to convert amides into nitriles.This chemistry provides a novel amide transformation pathway via both C–C and C–N bond cleavage.Interestingly,the simple,readily available,and inexpensive inorganic salt NaNO2 is successfully employed as a nitrogen source in this organic N-incorporation process.Applications of this study are demonstrated through the latestage modification of drug and natural product derivatives.展开更多
We describe an iron-catalyzed amide bond formation from readily available carboxylic acids and isocyanates.This method utilizes an abundant and biocompatible iron catalyst and easily accessible starting materials,gene...We describe an iron-catalyzed amide bond formation from readily available carboxylic acids and isocyanates.This method utilizes an abundant and biocompatible iron catalyst and easily accessible starting materials,generates CO_(2) as the only byproduct,and features broad substrate scopes with good functional group compatibility.Therefore,it provides a cost-effective and practical protocol to access a diverse variety of amides.展开更多
N-Acylpyrrole-type amides are a class of versatile building blocks in asymmetric synthesis.We report that by employing Ni(COD)2/2,2′-bipyridine(5 mol%)catalytic system,the direct,catalytic alcoholysis of N-acylpyrrol...N-Acylpyrrole-type amides are a class of versatile building blocks in asymmetric synthesis.We report that by employing Ni(COD)2/2,2′-bipyridine(5 mol%)catalytic system,the direct,catalytic alcoholysis of N-acylpyrrole-type aromatic and aliphatic amides with both primary and secondary alcohols can be achieved efficiently under very mild conditions(rt,1 h)even at gram scale.By increasing the catalyst loading to 10 mol%,prolonging reaction time(18 h),and/or elevating reaction temperature to 50°C/80°C,the reaction could be extended to both complex and hindered N-acylpyrroles as well as to N-acylpyrazoles,Nacylindoles,and to other(functionalized)primary and secondary alcohols.In all cases,only 1.5 equiv.of alcohol were used.The value of the method has been demonstrated by the racemization-free,catalytic alcoholysis of chiral amides yielded from other asymmetric methodologies.展开更多
文摘Methamphetamine (METH), a highly addictive drug used worldwide, induces oxidative stress in various animal organs. Recent animal studies indicate that methamphetamine also induces oxidative stress in the retina, which is an embryonic extension of the forebrain. The aim of this study, therefore, was to evaluate the protecttive effects of N-acetylcysteine amide (NACA) against oxidative stress induced by METH in retinal pigment epithelium (RPE) cells. Our studies showed that NACA protected against METH-induced oxidative stress in retinal pigment epithelial cells. Although METH significantly decreased glutathione (GSH) levels and increased reactive oxygen species (ROS) and malondialdehyde (MDA) levels, these returned to control levels with NACA treatment. Overall observations indicated that NACA protected RPE cells against oxidative cell damage and death by inhibiting lipid peroxidation, scavenging ROS, increasing levels of intracellular GSH, and maintaining the antioxidant enzyme activity and the integrity of the bloodretinal barrier (BRB). The effectiveness of NACA should be further evaluated to determine its potential for the treatment of numerous retinal diseases caused by oxidative stress.
文摘Glucocorticoids (GCs) are one of the most widely used immunosuppressive and anti-inflammatory agents. However, their long term and systemic use is associated with adverse drug reactions including posterior subcapsular cataracts as one of its ocular complications. Balanced redox state is crucial for maintenance of lens transparency, and a high content of glutathione (GSH) in the lens is believed to play a key role in doing so. Depletion of GSH is implicated in the etiopathogenesis of dexamethasone-induced cataracts and, therefore, the present study was sought to evaluate the efficacy of a novel thiol antioxidant, N-acetylcysteine amide (NACA), in preventing dexamethasone-induced cataractogenesis. Cataract formation was induced by incubation of rat lenses with 5 μM dexamethasone. To assess whether NACA had a significant impact on dexamethasone-induced cataracts, the rat lenses were divided into four groups: 1) control group (Dulbecco’s Modified Eagle Medium (DMEM), 2) dexamethasone group (DMEM with 5 μM dexamethasone), 3) NACA-only group (50 μM NACA solution), and 4) NACA pretreatment group (50 μM NACA for 6 hours followed by 5 μM dexamethasone only for 18 hours). Lenses were cultured for 7 days at 37°C under 5% CO2. Lenses were evaluated daily using a dissecting microscope and photographed and graded for the development of opacity. The rat lenses in both the control and the NACA-only groups were clear, whereas all lenses within the dexamethasone-only group developed well-defined cataracts. Overall observations indicated that NACA inhibits cataract formation by limiting lipid peroxidation and increasing the ratio of GSH/GSSG in lens. Therefore, NACA can be developed into a potential adjunctive therapeutic option for patients undergoing therapy with GCs to inhibit glucocorticoid-induced cataracts.
基金supported by the National Natural Science Foundation of China(No.21272086)
文摘The title compound 3-bromo-5-（4-chlorophenyl）-4-cyanopyrrole-N,N-dimethyl-2-amide（3） was synthesized with 4-bromo-2-（4-chlorophenyl）-5-（trifluoromethyl）-1H-pyrrole-3-carbonitrile（1） and N,N-dimethylformamide（2） by the α-C acylation reaction catalyzed by potassium t-butoxide, and characterized by IR, 1H-NMR and X-ray single-crystal diffraction. It crystallizes in monoclinic, space group P2（1/n）with a = 12.789（2）, b = 13.783（2）, c = 17.980（3） °, β = 109.230（3）°, V = 2992.5 A3, Mr = 352.62, Dc = 1.565 mg/m3, Z = 8, m = 2.924 mm-1, F（000） = 1408, the final R = 0.0424 and w R = 0.0973 for 3518 observed reflections with I 〉 2σ（I）. A total of 23559 reflections were collected, of which 6242 were independent（Rint = 0.0566）. The insecticidal, herbicidal and antibacterial activities of compound 3 were determined, and the experimental results showed that the mortality of 3 at the concentration of 100 ppm on the Fipronil against Linnaeus was 76.6%, the growth inhibition rate of 3 against Cynodon Dactylon under the condition of 100 ppm was 35.8% and the inhibitory activity of 3 at the concentration of 25 ppm against Fusarium graminearum reached 50.9%. Hence, the title compound has the value of further research and application prospect.
基金supported by the Key Tech-nologies R&D Program of China during the 11th Five-Year Plan period (2006BAD17B02)Central Public Research Institutes Basic Funds for Research and Development (Institute of Agro-Environmental Protection,Ministry of Agriculture), China
文摘A lab-incubation experiment was conducted to investigate the effects of different forms of nitrogen application （ammonium, NH4＋-N; nitrate, NO3--N; and amide-N, NH2-N） and different concentrations （40, 200 and 800 mg L-1） on N2O emission from the fluvo-aquic soil subjected to a freezing-thawing cycling. N2O emission sharply decreased at the start of soil freezing, and then showed a smooth line with soil freezing. In subject to soil thawing, N2O emission increased and reached a peak at the initial thawing stage. The average N2O emissions with addition of NH4＋-N, NO3 -N and NH2-N are 119.01, 611.61 and 148. 22 ug m-2 h-1, respectively, at the concentration of 40 mg L-1; 205.28, 1 084.40 and 106.13 ug m2 h-1 at the concentration of 200 mg L-1; and 693.95, 1 820.02 and 49.74 ug m-2 h4 at the concentration of 800 mg L-1. The control is only 100.35 ug m-2 h-1. N2O emissions with addition of NH4＋-N and NO3--N increased with increasing concentration, by ranging from 17.49 to 425.67% for NH4＋-N, and from 563.38 to 1458.6% for NO3--N compared with control. There was a timelag for N2O emission to reach a steady state with an increase of concentration. In contrast, by adding NH2-N to soil, N2O emission decreased with increasing concentration. In sum, NH4＋-N or NO3--N fertilizer incorporated in soil enhanced the cumulative N2O emission from the fluvo-aquic soil relative to amide-N. This study suggested that ammonium and nitrate concentration in overwintering water should be less than 200 and 40 mg L-1 in order to reduce N2O emissions from soil, regardless of amide-N.
基金the National Key R&D Program of China(grant no.2021YFA1501700)the NSFC(grant nos.22131002,22161142019,81821004),and the Tencent Foundation for financial support.
文摘Amides are among the fundamental chemicals in organic chemistry.Compared to other carbonyl functional groups,the transformation of amide is relatively difficult and remains a challenge.The traditional deconstruction transformations of amides to other functional products are usually limited to twisted or electronically activated amides.Herein,we describe a direct nitrogenation approach to convert amides into nitriles.This chemistry provides a novel amide transformation pathway via both C–C and C–N bond cleavage.Interestingly,the simple,readily available,and inexpensive inorganic salt NaNO2 is successfully employed as a nitrogen source in this organic N-incorporation process.Applications of this study are demonstrated through the latestage modification of drug and natural product derivatives.
基金the National Natural Science Foundation of China(2207118522271224)Wuhan University startup funding for financial support.
文摘We describe an iron-catalyzed amide bond formation from readily available carboxylic acids and isocyanates.This method utilizes an abundant and biocompatible iron catalyst and easily accessible starting materials,generates CO_(2) as the only byproduct,and features broad substrate scopes with good functional group compatibility.Therefore,it provides a cost-effective and practical protocol to access a diverse variety of amides.
基金supported by the National Natural Science Foundation of China(21931010)the National Key Research and Development Program of China(2017YFA0207302)the Program for Changjiang Scholars and Innovative Research Team in University of the Ministry of Education,China.
文摘N-Acylpyrrole-type amides are a class of versatile building blocks in asymmetric synthesis.We report that by employing Ni(COD)2/2,2′-bipyridine(5 mol%)catalytic system,the direct,catalytic alcoholysis of N-acylpyrrole-type aromatic and aliphatic amides with both primary and secondary alcohols can be achieved efficiently under very mild conditions(rt,1 h)even at gram scale.By increasing the catalyst loading to 10 mol%,prolonging reaction time(18 h),and/or elevating reaction temperature to 50°C/80°C,the reaction could be extended to both complex and hindered N-acylpyrroles as well as to N-acylpyrazoles,Nacylindoles,and to other(functionalized)primary and secondary alcohols.In all cases,only 1.5 equiv.of alcohol were used.The value of the method has been demonstrated by the racemization-free,catalytic alcoholysis of chiral amides yielded from other asymmetric methodologies.
