Reaction of 4,4’-(1,4-phenylene)bis(5-acetyl-6-methyl-2-thioxo-1,2-dihydropyridine-3-carbonitrile) (1) with methyl iodide afforded the 4,4’-(1,4-phenylene)bis(5-acetyl-6-methyl-2-(methylthio)nicotinonitrile) (2). Th...Reaction of 4,4’-(1,4-phenylene)bis(5-acetyl-6-methyl-2-thioxo-1,2-dihydropyridine-3-carbonitrile) (1) with methyl iodide afforded the 4,4’-(1,4-phenylene)bis(5-acetyl-6-methyl-2-(methylthio)nicotinonitrile) (2). The reaction of 2 with hydrazine hydrate followed by diazotization reaction af-forded the 1,1’-(1,4-phenylenebis(3-amino-6-methyl-1H-pyrazolo[3,4-b]pyridine-4,5-diyl))bis(e-than-1-one) (3) and 1,1’-(1,4-phenylenebis(3-(chlorodiazenyl)-6-methyl-1H-pyrazolo[3,4-b]-pyridine-4,5-diyl))bis(ethan-1-one) (4) respectively. On the other hand, reaction of 4 with malononitrile, 2-cyanoethanethioamide, ethyl acetoacetate, acetyl acetone, ethyl benzoylacetate, diethylmalonate, ethyl cyanoacetate and phenacylbromide aiming to build up pyrazolotriazine or pyrazole ring on the ring system of 4. Structures of all newly synthesized heterocyclic compounds in the present study were confirmed by considering the data of IR, 1H NMR, mass spectra as well as that of elemental analyses.展开更多
Objective This study investigated the effects of bis(2-butoxyethyl) phthalate(BBOP) on the onset of male puberty by affecting Leydig cell development in rats.Methods Thirty 35-day-old male Sprague-Dawley rats were ran...Objective This study investigated the effects of bis(2-butoxyethyl) phthalate(BBOP) on the onset of male puberty by affecting Leydig cell development in rats.Methods Thirty 35-day-old male Sprague-Dawley rats were randomly allocated to five groups mg/kg bw per day that were gavaged for 21 days with BBOP at 0, 10, 100, 250, or 500 mg/kg bw per day. The hormone profiles;Leydig cell morphological metrics;mRNA and protein levels;oxidative stress;and AKT,mTOR, ERK1/2, and GSK3β pathways were assessed.Results BBOP at 250 and/or 500 mg/kg bw per day decreased serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels mg/kg bw per day(P < 0.05). BBOP at 500 mg/kg bw per day decreased Leydig cell number mg/kg bw per day and downregulated Cyp11a1, Insl3, Hsd11b1,and Dhh in the testes, and Lhb and Fshb mRNAs in the pituitary gland(P < 0.05). The malondialdehyde content in the testis significantly increased, while Sod1 and Sod2 mRNAs were markedly downregulated, by BBOP treatment at 250–500 mg/kg bw per day(P < 0.05). Furthermore, BBOP at 500mg/kg bw per day decreased AKT1/AKT2, mTOR, and ERK1/2 phosphorylation, and GSK3β and SIRT1levels mg/kg bw per day(P < 0.05). Finally, BBOP at 100 or 500 μmol/L induced ROS and apoptosis in Leydig cells after 24 h of treatment in vitro(P < 0.05).Conclusion BBOP delays puberty onset by increasing oxidative stress and apoptosis in Leydig cells in rats.The graphical abstract is available on the website www.besjournal.com.展开更多
Bis(15-crown-5)-stilbenes containing crown ether parts have been widely used in a variety of chemical applications,such as cation detectors,because of their ability to selectively bind to alkali metal cations,Bis(15-c...Bis(15-crown-5)-stilbenes containing crown ether parts have been widely used in a variety of chemical applications,such as cation detectors,because of their ability to selectively bind to alkali metal cations,Bis(15-crown-5)-stilbenes and its derivatives with complexation of one-or two-alkali metal cation(Li^(+),Na^(+)and K^(+))have been theoretically investigat-ed by quantum chemistry methods.The coordination of alkali cations results in partial shrinkage of crown ethers,which directly affected natural distribution analysis charges and molecular orbital energy levels.The number of alkali metal ions has significant effects on absorption spectra and mean second hyperpolarizability.When one alkali metal ion was added to the anticonformer of bis(15-crown-5)-stilbene,the absorption spectra were obvious-ly redshifted and the mean second hyperpolarizability values were slightly increased;while two alkali metal ions were added to bis(15-crown-5)-stilbene,the absorption spectra were ob-viously blue shifted and the mean second hyperpolarizability values decreased.On the other hand,as the radius of the alkali ions increased,the mean second hyperpolarizability values of the compounds increased gradually.It is indicated that the mean second hyperpolarizability value is sensitive to the number and radius of the alkali metal cations,thus the third order nonlinear optical response can be used as a signal to detect the number and type of alkali met-al ions.展开更多
文摘Reaction of 4,4’-(1,4-phenylene)bis(5-acetyl-6-methyl-2-thioxo-1,2-dihydropyridine-3-carbonitrile) (1) with methyl iodide afforded the 4,4’-(1,4-phenylene)bis(5-acetyl-6-methyl-2-(methylthio)nicotinonitrile) (2). The reaction of 2 with hydrazine hydrate followed by diazotization reaction af-forded the 1,1’-(1,4-phenylenebis(3-amino-6-methyl-1H-pyrazolo[3,4-b]pyridine-4,5-diyl))bis(e-than-1-one) (3) and 1,1’-(1,4-phenylenebis(3-(chlorodiazenyl)-6-methyl-1H-pyrazolo[3,4-b]-pyridine-4,5-diyl))bis(ethan-1-one) (4) respectively. On the other hand, reaction of 4 with malononitrile, 2-cyanoethanethioamide, ethyl acetoacetate, acetyl acetone, ethyl benzoylacetate, diethylmalonate, ethyl cyanoacetate and phenacylbromide aiming to build up pyrazolotriazine or pyrazole ring on the ring system of 4. Structures of all newly synthesized heterocyclic compounds in the present study were confirmed by considering the data of IR, 1H NMR, mass spectra as well as that of elemental analyses.
基金supported by the National Natural Science Fund of China[no.81730042]。
文摘Objective This study investigated the effects of bis(2-butoxyethyl) phthalate(BBOP) on the onset of male puberty by affecting Leydig cell development in rats.Methods Thirty 35-day-old male Sprague-Dawley rats were randomly allocated to five groups mg/kg bw per day that were gavaged for 21 days with BBOP at 0, 10, 100, 250, or 500 mg/kg bw per day. The hormone profiles;Leydig cell morphological metrics;mRNA and protein levels;oxidative stress;and AKT,mTOR, ERK1/2, and GSK3β pathways were assessed.Results BBOP at 250 and/or 500 mg/kg bw per day decreased serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels mg/kg bw per day(P < 0.05). BBOP at 500 mg/kg bw per day decreased Leydig cell number mg/kg bw per day and downregulated Cyp11a1, Insl3, Hsd11b1,and Dhh in the testes, and Lhb and Fshb mRNAs in the pituitary gland(P < 0.05). The malondialdehyde content in the testis significantly increased, while Sod1 and Sod2 mRNAs were markedly downregulated, by BBOP treatment at 250–500 mg/kg bw per day(P < 0.05). Furthermore, BBOP at 500mg/kg bw per day decreased AKT1/AKT2, mTOR, and ERK1/2 phosphorylation, and GSK3β and SIRT1levels mg/kg bw per day(P < 0.05). Finally, BBOP at 100 or 500 μmol/L induced ROS and apoptosis in Leydig cells after 24 h of treatment in vitro(P < 0.05).Conclusion BBOP delays puberty onset by increasing oxidative stress and apoptosis in Leydig cells in rats.The graphical abstract is available on the website www.besjournal.com.
基金surported by the Jilin Province Science and Technology Development Project(No.20220203017SF)Industrialization Project of the 13th Five-Year"Education Department of Jilin Province(No.JJKH20200334KJ)the National Natural Sci-ence Foundation of China(No.11704143).
文摘Bis(15-crown-5)-stilbenes containing crown ether parts have been widely used in a variety of chemical applications,such as cation detectors,because of their ability to selectively bind to alkali metal cations,Bis(15-crown-5)-stilbenes and its derivatives with complexation of one-or two-alkali metal cation(Li^(+),Na^(+)and K^(+))have been theoretically investigat-ed by quantum chemistry methods.The coordination of alkali cations results in partial shrinkage of crown ethers,which directly affected natural distribution analysis charges and molecular orbital energy levels.The number of alkali metal ions has significant effects on absorption spectra and mean second hyperpolarizability.When one alkali metal ion was added to the anticonformer of bis(15-crown-5)-stilbene,the absorption spectra were obvious-ly redshifted and the mean second hyperpolarizability values were slightly increased;while two alkali metal ions were added to bis(15-crown-5)-stilbene,the absorption spectra were ob-viously blue shifted and the mean second hyperpolarizability values decreased.On the other hand,as the radius of the alkali ions increased,the mean second hyperpolarizability values of the compounds increased gradually.It is indicated that the mean second hyperpolarizability value is sensitive to the number and radius of the alkali metal cations,thus the third order nonlinear optical response can be used as a signal to detect the number and type of alkali met-al ions.
