The cytochrome bc1complex(the bc1complex or complex Ⅲ) is an attractive target for the discovery of numerous pharmaceuticals and pesticides. In order to identify new lead structures for this target, a new series of m...The cytochrome bc1complex(the bc1complex or complex Ⅲ) is an attractive target for the discovery of numerous pharmaceuticals and pesticides. In order to identify new lead structures for this target, a new series of molecules, N-(4-aryloxyphenyl)phthalimides, were designed and synthesized in a straightforward manner. Our design strategy was to introduce a 4-aryloxyphenyl group, a fragment which exhibited promising bc1complex-inhibiting properties, into the aryl group of the valuable N-arylphthalimide backbone. Afterward, the biochemical evaluation of the newly synthesized compounds was carried out,and the results implied that several compounds demonstrated good activities against succinatecytochrome reductase(SCR, a mixture of mitochondrial complex Ⅱ and the bc1complex). Further studies confirmed that 3e’, a representative compound in this paper, was identified as an inhibitor of the bc1complex. Furthermore, computational simulations were also performed to better understand binding of 3e’ to the enzyme complex, which indicated that 3e’ should bind to the Qosite of the bc1complex.Consequently, we harbor the idea that this paper can provide a solid platform for synthesis and discovery of other bc1complex inhibitors.展开更多
The effect of Co complexes with a Schiff base ligand on the electrochemical corrosion behavior of 316 L SS in 0.1 M H<sub>2</sub>SO<sub>4</sub> at 25℃ has been investigated at various inhibito...The effect of Co complexes with a Schiff base ligand on the electrochemical corrosion behavior of 316 L SS in 0.1 M H<sub>2</sub>SO<sub>4</sub> at 25℃ has been investigated at various inhibitor concentration using electrochemical techniques (impedance spectroscopy (EIS), polarization curves). Corrosion measurements indicate that Co complex act as moderately inhibitors. Results revealed that increasing the concentration of Co complex increases the corresponding IE% values till 100 ppm. Co complex acts as mixed type inhibitors with predominant effect on the anodic dissolution of iron. Adsorption studies showed that the process follows Langmuir adsorption isotherm.展开更多
Human 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) catalyzes the biosynthesis of the most potent natural estrogen 17β-estradiol (E2) from estrone (E1) in the ovary and peripheral tissues, playing a pivotal ro...Human 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) catalyzes the biosynthesis of the most potent natural estrogen 17β-estradiol (E2) from estrone (E1) in the ovary and peripheral tissues, playing a pivotal role in the progression of estrogen-dependent diseases. N-n-Butyl-N-methyl-ll-(16'α-chloro-3',17'β-dihydroxyestra-1',3',5'(10')-trien-7'α-yl)undecanamide (EM-139) was previously described as a dual-site inhibitor that can inhibit 17β-HSD1 transforming E1 into E2 and also inhibit estrogen receptor. In the present report, we describe the co-crystallization of EM-139 with 17β-HSD1 as well as the analysis of the three-dimensional structure of the enzyme/inhibitor complex. The crystal is grown under similar condition as native crystals, whereas the space group is changed to I121 never observed in other 17β-HSD1 crystals before. The steroidal moiety of the bound EM-139 molecule has shown a binding pattern similar to E2 in the E2 binary complex. The O-3 of the inhibitor develops hydrogen bonds with residues His221 and Glu282, whereas the O-17 makes hydrogen bonds with Ser142 and Tyr155. The bulky 7α-alkyl moiety of the inhibitor, which is essential for its anti-estrogenic activity but cannot be defined in the electron density, may compromise the inhibitory effect of EM-139 to 17β-HSD1. Moreover, the 16α-Cl atom shows no obvious interaction with surrounding residues. The atomic level understanding of the inhibitory mechanism of EM-139 provides important information for the inhibitor design of 17β-HSD1, which will facilitate future development of more potent and selective inhibitors of the enzyme for therapeutic purposes.展开更多
The structure of the complex of mung bean trypsin inhibitor lysine active fragment with bovine trypsin has been determined at a resolution of 1.8 A by A-ray crystallographic analysis and the complex model refined by r...The structure of the complex of mung bean trypsin inhibitor lysine active fragment with bovine trypsin has been determined at a resolution of 1.8 A by A-ray crystallographic analysis and the complex model refined by restrained least-squares minimization with the data between 10 and 1.8 resolution.The current conventional R factor is 17.3%,and the model con- tains 1648 protein atoms,219 inhibitor atoms and 126 water molecules.The most prominent feature of the inhibitor fragment is that it does not contain any alpha-helices.Most of the chain fold in an irregular fashion.The seven residues of the binding segment of the inhibitor lysine active frag- ment are in specific contact with bovine trypsin.The binding interaction and geometry around the reactive site are similar to that observed in other studies of trypsin-inhibitor complexes.展开更多
A novel copper（II） complex with the reduced Schiff base, [Cu（L）2]·H2O （I, HL = N-（4-hydroxybenzyl）-L-serine）, was prepared in aqueous solution and characterized by elemental analysis, FT-IR, electrospray ...A novel copper（II） complex with the reduced Schiff base, [Cu（L）2]·H2O （I, HL = N-（4-hydroxybenzyl）-L-serine）, was prepared in aqueous solution and characterized by elemental analysis, FT-IR, electrospray ionization mass spectrometry and single-crystal X-ray diffraction. Complex I crystallizes in the orthorhombic system, space group P212121, with a = 8.9040（18）, b = 9.1530（18）, c = 24.891（5）A^°, V = 2028.6（7） A^°3, Z = 4, C20H26CuN2O9, Mr = 501.97, Dc = 1.644g·cm^3, μ = 1.135 mm^-1, F（000） = 1044, GOOF = 1.194, the final R = 0.0484 and wR = 0.1420 for 6186 observed reflections （I 〉 2σ（I））. In I, two L^- anions are coordinated to the copper ion in tridentate and bidentate chelating modes, respectively, resulting in the coordinated geometry of copper ion to be a distorted square pyramid. The intermolecular hydrogen bonds between the complexes, complexes and lattice water molecules lead to a 2D supramolecular network. The bioactivity of the complex as a potential PTPs inhibitory agent in vitro was investigated, displaying potent inhibition against PTP1B （IC50, 0.27 μM） and TCPTP （IC50, 0.57 μM） with a moderate selectivity.展开更多
基金supported by the National Natural Science Foundation of China(Nos.21502062,21272091 and 21472063)Hubei Provincial Department of Education(No.Q20102606)+3 种基金Xiangyang Science and Technology Bureau(No.2010GG1B33)Structural Biomedicine and Pharmacochemistry of Hubei University of Arts and Sciencethe support from the Russian Foundation for Basic Research(No.18-29-04047)the Tomsk Polytechnic University Competitiveness Enhancement Program grant(No.VIU-195/2018)
文摘The cytochrome bc1complex(the bc1complex or complex Ⅲ) is an attractive target for the discovery of numerous pharmaceuticals and pesticides. In order to identify new lead structures for this target, a new series of molecules, N-(4-aryloxyphenyl)phthalimides, were designed and synthesized in a straightforward manner. Our design strategy was to introduce a 4-aryloxyphenyl group, a fragment which exhibited promising bc1complex-inhibiting properties, into the aryl group of the valuable N-arylphthalimide backbone. Afterward, the biochemical evaluation of the newly synthesized compounds was carried out,and the results implied that several compounds demonstrated good activities against succinatecytochrome reductase(SCR, a mixture of mitochondrial complex Ⅱ and the bc1complex). Further studies confirmed that 3e’, a representative compound in this paper, was identified as an inhibitor of the bc1complex. Furthermore, computational simulations were also performed to better understand binding of 3e’ to the enzyme complex, which indicated that 3e’ should bind to the Qosite of the bc1complex.Consequently, we harbor the idea that this paper can provide a solid platform for synthesis and discovery of other bc1complex inhibitors.
文摘The effect of Co complexes with a Schiff base ligand on the electrochemical corrosion behavior of 316 L SS in 0.1 M H<sub>2</sub>SO<sub>4</sub> at 25℃ has been investigated at various inhibitor concentration using electrochemical techniques (impedance spectroscopy (EIS), polarization curves). Corrosion measurements indicate that Co complex act as moderately inhibitors. Results revealed that increasing the concentration of Co complex increases the corresponding IE% values till 100 ppm. Co complex acts as mixed type inhibitors with predominant effect on the anodic dissolution of iron. Adsorption studies showed that the process follows Langmuir adsorption isotherm.
文摘Human 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) catalyzes the biosynthesis of the most potent natural estrogen 17β-estradiol (E2) from estrone (E1) in the ovary and peripheral tissues, playing a pivotal role in the progression of estrogen-dependent diseases. N-n-Butyl-N-methyl-ll-(16'α-chloro-3',17'β-dihydroxyestra-1',3',5'(10')-trien-7'α-yl)undecanamide (EM-139) was previously described as a dual-site inhibitor that can inhibit 17β-HSD1 transforming E1 into E2 and also inhibit estrogen receptor. In the present report, we describe the co-crystallization of EM-139 with 17β-HSD1 as well as the analysis of the three-dimensional structure of the enzyme/inhibitor complex. The crystal is grown under similar condition as native crystals, whereas the space group is changed to I121 never observed in other 17β-HSD1 crystals before. The steroidal moiety of the bound EM-139 molecule has shown a binding pattern similar to E2 in the E2 binary complex. The O-3 of the inhibitor develops hydrogen bonds with residues His221 and Glu282, whereas the O-17 makes hydrogen bonds with Ser142 and Tyr155. The bulky 7α-alkyl moiety of the inhibitor, which is essential for its anti-estrogenic activity but cannot be defined in the electron density, may compromise the inhibitory effect of EM-139 to 17β-HSD1. Moreover, the 16α-Cl atom shows no obvious interaction with surrounding residues. The atomic level understanding of the inhibitory mechanism of EM-139 provides important information for the inhibitor design of 17β-HSD1, which will facilitate future development of more potent and selective inhibitors of the enzyme for therapeutic purposes.
文摘The structure of the complex of mung bean trypsin inhibitor lysine active fragment with bovine trypsin has been determined at a resolution of 1.8 A by A-ray crystallographic analysis and the complex model refined by restrained least-squares minimization with the data between 10 and 1.8 resolution.The current conventional R factor is 17.3%,and the model con- tains 1648 protein atoms,219 inhibitor atoms and 126 water molecules.The most prominent feature of the inhibitor fragment is that it does not contain any alpha-helices.Most of the chain fold in an irregular fashion.The seven residues of the binding segment of the inhibitor lysine active frag- ment are in specific contact with bovine trypsin.The binding interaction and geometry around the reactive site are similar to that observed in other studies of trypsin-inhibitor complexes.
基金Supported by NNSFC(Nos.21271121,21471092,21571118)
文摘A novel copper（II） complex with the reduced Schiff base, [Cu（L）2]·H2O （I, HL = N-（4-hydroxybenzyl）-L-serine）, was prepared in aqueous solution and characterized by elemental analysis, FT-IR, electrospray ionization mass spectrometry and single-crystal X-ray diffraction. Complex I crystallizes in the orthorhombic system, space group P212121, with a = 8.9040（18）, b = 9.1530（18）, c = 24.891（5）A^°, V = 2028.6（7） A^°3, Z = 4, C20H26CuN2O9, Mr = 501.97, Dc = 1.644g·cm^3, μ = 1.135 mm^-1, F（000） = 1044, GOOF = 1.194, the final R = 0.0484 and wR = 0.1420 for 6186 observed reflections （I 〉 2σ（I））. In I, two L^- anions are coordinated to the copper ion in tridentate and bidentate chelating modes, respectively, resulting in the coordinated geometry of copper ion to be a distorted square pyramid. The intermolecular hydrogen bonds between the complexes, complexes and lattice water molecules lead to a 2D supramolecular network. The bioactivity of the complex as a potential PTPs inhibitory agent in vitro was investigated, displaying potent inhibition against PTP1B （IC50, 0.27 μM） and TCPTP （IC50, 0.57 μM） with a moderate selectivity.
基金National Natural Science Foundation of China(No.52101084)Guangdong Basic and Applied Basic Research Foundation,China(Nos.2023A1515011579,2020A1515110754)Guangzhou Basic and Applied Basic Research Foundation,China(No.202102020612)。
