Identification of Chinese Herbal Compounds with Potential as JAK3 Inhibitors.

The Janus kinases (JAKs) consist of four similar tyrosine kinases and function as key hubs in the signaling pathways that are implicated in both innate and adaptive immunity. Among the four members, JAK3 is probably the more attractive target for treatment of inflammatory diseases because its inhibition demonstrates the greatest immunosuppression and most profound effect in the treatment of such disorders. Although many JAK3 inhibitors are already available, certain shortcomings have been identified, mostly acquired drug resistance or unwanted side effects. To discover and identify new promising lead candidates, in this study, the structure of JAK3 (3LXK) was obtained from the Protein Data Bank and used for simulation modeling and protein-ligand interaction analysis. The ~36,000 Chinese herbal compounds obtained from TCM Database@Taiwan were virtually screened by AutoDock Vina docking program and filtered with Lipinski's Rules and ADME/T virtual predictions. Because of high occurrence of fake hits during docking, we selected 12 phytochemicals which have demonstrated modulating JAKs expressions among the top 50 chemicals from docking results. To validate whether these compounds are able to directly mediate JAK3 kinase, we have investigated the inhibitory activity using enzymatic activity assays, western blot, and HEK 293 cell STAT5 transactivity assays. The molecular analysis included docking and molecular dynamics (MD) simulations in order to investigate structural conformations and to explore the key amino acids in the interaction between JAK3 kinase and its putative ligands. The results demonstrated that Cryptotanshinone, Icaritin, and Indirubin exhibited substantial inhibitory activity against JAK3 kinase in vitro. The results also provide binding models of the protein-ligand interaction, detailing the interacting amino acid residues at the active ATP-binding domains of JAK3 kinase. In conclusion, our work discovered 3 potential natural inhibitors of JAK3 kinase and could provide new possibilities and stimulate new insights for the treatment of JAK3-targeted diseases.

[Non-covalent albumin conjugates of silicon (IV) phthalocyanines axially substituted with nucleoside: preparation and in vitro photodynamic activities].

The interactions of bovine serum albumin (BSA) with five novel silicon (N) phthalocyanines(SiPcl-5) axially modified by nucleosides (cytidine, 5-N-cytidine, methyl cytidine, uridine and methyl uridine) derivatives were studied by fluorescence spectroscopy. The results show that there are strong interactions between these silicon phthalocyanines and BSA with a binding constant of (4.90-83.18) x 10(5) mol(-1) x L. Therefore, the non-covalent BSA conjugate of bis(2', 3'-O-isopropyl-cytidine-oxy) phthalocyaninatosilicon(IV) (SiPc1) was further been prepared. The molar ratio of phthalocyanine to albumin was found to be 1:1 for the obtained SiPcl-BSA conjugate. The absorption spectra of SiPc1 and SiPc1-BSA in the visible region have no significant difference, both showing an Q-band maximum at about 686 nm. It indicates that the spectroscopic characteristics of SiPc1 are not affected by binding to albumin. The SiPcl-BSA conjugate exhibits high photodynamic activity against human hepatoma cell line HepG2 with an IC50 value of 3.0 x 10(-7) mol x L(-1). By comparsion, SiPc1-BSA has a higher photodynamic activity than SiPc1 (in PBS formation, IC50 = 7.0 x 10(-7) mol x L(-1)), which can be attributed to its higher cellular uptake.

[Spectral properties, photodynamic anticancer activity and the interaction with albumin of silicon phthalocyanine axially modified by pyrimidine derivatives].

Photophysical photochemical properties, in vitro photodynamic anticancer activity and interaction with albumin of a new axially modified silicon phthalocyanine, i. e. di (2-amino-6-trifluoromethyl-4-pyrimidinyloxy) silicon phthalocyanine (SiPcF), were studied in the present paper. The Q band maximum absorption of SiPcF located at 686 nm with the molar absorption coefficient of 2.3 x 10(5) mol(-1) * L * cm(-1). The fluorescence emission of SiPcF peaked at 694 nm with a fluorescence quantum yield of 0.46. Its singlet oxygen quantum yield produced by photosensitization is 0.38, suggesting that SiPcF is an effective 1O2 photosensitizer. There is strong interaction between SiPcF and bovine serum albumin (BSA). The binding constant is 4.33 x 10(5) mol X L(-1) and the number of binding sites is 1. In vitro experiments show that SiPcF had a high photodynamic anticancer activity against human hepatoma cells HepG2 with an IC50 value down to 5 x 10(-7) mol X L(-1).

[Synthesis and photodynamic anticancer activity of silicon phthalocyanine axially modified by nucleoside derivatives].

A new axially modified silicon phthalocyanine, di [5'-(2', 3'-O-isopropyl)-5-methyl cytidineoxy] silicon phthalocyanine (SiPcG), was prepared and characterized by 1H NMR and HRMS. This compound is essentially nonaggregated in N,N-dimethyformamide and 1% cremophor EL aqueous solution. It shows a Qband at 676 nm and fluorescence emission at 685 nm in DMF, and exhibits a Q-band at 679 nm and fluorescence emission at 689 nm in 1% cremophor EL aqueous solution. The SiPcG shows a high photodynamic activity against human hepatoma cells HepG2 with an IC50 value down to 7.8 x 10(-8) mol x L(-1). Fluorescence confocal microscopy study indicated that the SiPcG locates preferentially in the mitochondria of cells. The research results show that the SiPcG is highly potential as a new anti-cancer photosensitizer.

[Synthesis, structure and special study of 1D cadmium sulfate-H2biim coordination polymer].

A novel cadmium complexes of {[Cd(H2 biim)2 (SO4)] x 3H2O}n(1) (H2 biim = 2,2'-biimidazole) was synthesized by hydrothermal reaction of 3CdSO4 x 8H2O and 2,2'-biimidazole ligand. The complex was built up by [Cd(H2 biim)2]2+ units bridged sequentially by SO4(2-) anions to form 1D zigzag chains parallel to the c-axis. The H2biim ligands were attached to the 1D chain as branches of the chain by coordinating to Cd2+ at two sides of the chain. The chains were held together by pi--pi interaction and O--H***O interactions, thus yielding a 3D extended supramolecular network The responses of symmetric stretching vibration of SO4(2-), N--C single bond, N==C double bond and anti-symmetric stretching vibration of N-C single bond were detected in 2D IR correlation spectra under thermal perturbation. The complex exhibited strong blue emission peak at 498 nm (lambda(ex) x = 397 nm) that can be assigned to a ligand-to-metal charge-transfer (LMCT) band.

[Structural and spectral study of a novel lanthanide 2-hydroxynicotinic acid coordination polymer].

A novel lanthanide 2-hydroxynicotinic acid coordination polymer 1 {[LaL(HL) (H2O)3]1/3 (SO4)2/3 (H3O)2 H2O} (H2 L = 2-hydroxynicotinic acid) has been synthesized under hydrothermal condition and characterized by crystal X-ray diffraction, IR, UV, TGA, two-dimensional infrared (2D IR) correlation spectroscopy with magnetic and thermal perturbation. In 1, La ions are connected by 2-hydroxynicotinic acid through both carboxylate oxygen atoms and oxygen atoms from hydroxyl group in pyridine to generate a 2D layer in the ab plane, these layers are further connected by weak interactions to form a 3D framework along c axis. The response of out-of-plane bending vibrations of N-H and C-H are remarkable in the 2D IR correlation spectra under magnetic perturbation, this may attributes to the inducement of pi-electron cloud deformation under magnetic perturbation, v4 vibrations from SO4(2-) was also sensitive to magnetic perturbation. In addition, stretching vibrations from N-H are sensitive to thermal perturbation.

[Synthesis and spectroscopic properties of covalent albumin conjugates of phthalocyanine zincs substituted with metadicarboxyphenoxyl groups].

Four kinds of covalent serum albumin (BSA or HSA) conjugates of beta-tetrakis[(3,5-dicarboxy)phenoxy]-phthalocyaninatozinc (1) and beta-octakis [(3, 5-dicarboxy) phenoxy]-phthalocyaninatozinc (2) were synthesized by the approach of amide bond. The molar ratio of phthalocyanine to albumin in conjugates were found to be 6 - 7.1. Their absorption spectra were measured in PBS solution. When conjugated to albumin, compound 1 displays more distinct monomer absorption characteristics (with the maximum absorption at 677 nm) than its free form. Compound 2 in albumin framework exists mostly in monomer form, which is beneficial to photodynamic therapy in aqueous solution. Both 2-BSA and 2-HSA show a sharp and intense Q-band at 681 nm and 682 nm with the molar extinction coefficient of 2.01 x 10(5) and 2.05 x 10(5) mol(-1) L cm(-1) respectively. The Q-band absorption spectra and existent state of phthalocyanine 1 or 2 in conjugates were not affected by the pH value of aqueous solution, which are obviously different from that of the corresponding free phthalocyanine.

[Influence of albumin on the spectroscopic properties and existence state of mono-substituted phthalocyanine zinc (II)].

Interaction between 1-[4-(2-carboxyl-ethyl-)phenoxy] phthalocyanine Zinc(II) (ZnPcC1) and albumin (human serum albumin or bovine serum albumin) was studied. ZnPcC1 can be covalently bound to albumin through amide bond formation. The molar ratios of ZnPcC1 to albumins are found to be about 7 : 1 in the covalent bioconjugates. On the other hand, there are strong non-covalent interactions between ZnPcC1 and albumins with a binding constant of ca. 1.0 x 10(5) mol(-1) x L. Binding sites competition experiments suggest that the binding site locates in subdomain I B of human serum albumin. When conjugated to albumin, no matter covalent conjugation or non-covalent conjugation, the ZnPcC1 exhibit more distinctive characteristic monomer absorption than the free ZnPcC1, which is a property beneficial to photodynamic therapy. Covalent conjugation results in the Q-band of ZnPcC1 red-shifting about 5 nm, whereas non-covalent conjugation does not lead to red-shift.

[The structure and spectral research on Mn2 [V12 B16 O52 (OH)6 ] (en) 2 (H3O)6 (H2O)5 (en = ethylenediamine)].

A novel polyoxovanadium borate Mn2[V12B16O52 (OH)6](en)2 (H3O)6 (H2O)5 1(en = ethylenediamine) was hydrothermally synthesized and characterized by IR, two-dimensional infrared (2D IR) correlation spectroscopy with magnetic and thermal perturbation, and single crystal X-ray diffraction. In 1, it is interesting that each [V12B16O52 (OH)6]14- units is connected by four [Mn(H2O)2]2+ to generate a 2D layer on the ab plane. Along c axis, these layers are further linked by H-bond to form a 3D framework. The response of the stretching vibrations of B-O, V-O-V and Mn-O-B was detected in the 2D IR correlation spectra with magnetic perturbation. In addition, the response of the stretching vibrations of B-OH, B-O, V-O-V and Mn-O-B was detected in the 2D IR correlation spectra with thermal perturbation.

[Synthesis, spectral analysis and photocatalysis of Ag/K4Nb6,O17 heterojunction catalysts].

K4Nb6O17 photocatalyst was successfully synthesized by low-temperature hydrothermal method with layer structure. Considering that a large number of hydroxyl (Nb-OH) and oxygen species (Nb==O, Nb--O-) exist on the surface of K4Nb6O17 synthesized by hydrothermal method, Ag(en)2+ precursors were employed to synthesize Ag/K4Nb6O17 heterostructure photo-catalysts with highly dispersed Ag. Photocatalytic performance evaluation results show that the photodegradation rate of MO for K4Nb6O17 was remarkably improved when a small amont of Ag was loaded. The best loading dose of Ag is 0.5 at%. Based on various characterizations results of XRD, FTIR, UV-Vis DRS, XRF and TEM, the photocatalytic mechanism of Ag/ K4Nb6O17 heterostructure catalysts was illuminated in detail and the conclusions were drawn as follows: (1) K4Nb6O17 nanocrystals serve as electron and hole sources for degradation of an organic dye; (2) Ag nanoparticles on the surface of K4Nb6O17 nanocrystals act as a sink for the electrons, promote interfacial charge-transfer kinetics between the metal and semiconductor, improve the separation of photogenerated electron-hole pairs, and thus enhance the photocatalytic activity of Ag/K4Nb6O17 photocatalyst.

[Syntheses and spectral study of novel metal zinc organic phosphonate].

Two novel Zn2+ organic phosphonate Zn(4,4'-bipy)(HBCP) 1 and [Zn2 (phen)2 (BCP)(H2 BCP)].H2O2 were hydrothermally synthesized. The compound 1 is with two-dimensional layer framework whereas the compound 2 is zero-dimensional structure. The Zn2+ ion is four-coordinated in compound 1 while five or six-coordinated in compound 2. The relationship between their properties and structures was studied by using FTIR, two-dimensional (2D) correlation infrared spectroscopy under thermal perturbation, fluorescence and UV-Vis DRS spectrum etc. Upon light excitation at 350 nm, the compound 1 exhibits luminescence with a strong wide emission at 412 nm and a weak emission at 520 nm, while the compound 2 exhibits luminescence with a wide emission only at 398 nm under light excitation at 336 nm.

[Structural and spectral study of a novel rare-earth and 3-bi-pyridine acid polymer].

A novel zero-dimension coordination polymer Gd2 (In)6 (H2O)4 (1) (In = 3-bipyridine acid) was synthesized under hydrothermal condition. By the analysis of single-crystal X-ray diffraction, the structure of the compound is that two Gd atoms connect with zero-dimension bi- nucleus cluster by the bridged carboxylate of four Ins. Based on the determination of the structure, the 2D correlation FTIR spectra with the perturbations of magnetism and thermal was applied. Under the perturbations of temperature, the vibration of the carboxylate has the very strong response, which is related with the strong coordinating ability of the carboxylate. At the same time, due to the different coordinated mode of the carboxylate with Gd, the response of Gd--O bonds is different under the temperature perturbations. Under the perturbations of magnetism, the vibration of the carboxylate has also the very strong response, which may be related with one-negetive charge of the carboxylate. The 2D correlation ultraviolet spectral with the perturbation of magnetism were investigated. Compared with one-dimension ultraviolet spectral, the transition of the pi electrons in bi-pyridine ring and the charge transition from ligand to the metal have the very strong response. At the same time, the fluorescence spectral and TGA were studied.

[Studies on Ag-TiO2/KIT-6 composite nanosized photocatalyst].

In the present paper, ordered mesoporous silica (KIT-6) as support, nanosized TiO2 into KIT-6 was synthesized by titanium tetraisopropoxide hydrolysis. Then silver was loaded by deposition-precipitation method. Ag-TiO2/KIT-6 composite nanosized photocatalyst was firstly synthesized and a series of correlated catalysts were synthesized by the same preparation method. Methyl orange is presently adopted as a representative organic pollutant to evaluate the photocatalytic performance of the as-synthesized catalysts. The order of photocatalytic activity of the as-synthesized samples was found as Ag-TiO2/KIT-6 > Ag/TiO2 > TiO2/KIT-6 > TiO2 > Ag/KIT-6. Detailed characterizations were conducted by techniques including XRD, N2 physical adsorption, XPS, UV-Vis DRS and TEM. It was found that the Ag-TiO2 /KIT-6 sample shows the highest photocatalytic activity, which should be attributed to the Ag-TiO2 heterojunction structure and higher BET surface area of the Ag-TiO2/KIT-6 sample. Ag-TiO2 heterojunction improves the separation of photogenerated electron-hole pairs, thus enhancing the photocatalytic activity; Ag-TiO2/KIT-6 sample possesses high BET surface area, which facilitates adsorption and transportation of dye molecules, also leading to higher photocatalytic activity.

[Study on the spectra of Au/alpha-Fe2O3 catalysts modified by ZrO2 and Nb2O5 promoters].

A series of Au/alpha-Fe2O3 catalysts promoted with ZrO2 and Nb2O5 were prepared by parallel co-precipitation method. Detailed characterizations were conducted by techniques including UV-Vis-DRS, XPS, TEM and XRF. Results indicated that the enrichment of Au, ZrO2 and Nb2O5 on the surface induced by the strong interaction between ZrO2 and Nb2O5 kept the nanoparticles apart, delaying sintering. Performance tests carried out in the reformed methanol steam showed that its CO conversion almost reached the maximum value of 99% at 200 degrees C, and maintained a better stability compared with unmodified samples within 50 h on-stream. All these indicated that ZrO2 and Nb2O5 promoters efficiently improved the performance of the Au/alpha-Fe2O3 catalysts.

[2D correlation spectral study of a coordination polymer [Eu(PCPOA)3 (H2O)]n].

A novel two dimensional coordination polymer [Eu(PCPOA)3 (H2O)], was synthesized under hydrothermal condition. Based on the determination of the structure, the 2D correlation FTIR spectra with the perturbation of magnetism and the 2D correlation fluorescence spectra with the perturbation of temperature were investigated. The energy bonds were calculated using CASTEP Program of Material studio. The Europium ions are nine-coordinated and the ligands adopted two different modes to connect the Eu3+ ions to 2D layer structure. The study of the 2D-FTIR reveals that the carboxylates coordinate with the center ions not only as monodentate, but also as bidentate chelate. The 2D fluorescence spectra indicates that the transition of (5)D0-->(7)F2 is influenced intensively by the perturbation of temperature.

[Synthesis and spectral study of three polyoxovanadium clusters].

Three polyoxovanadium clusters, [{Ni(phen)}2 V4O12] x H2O I, [N(CH2CH2)3NH]Na(H2O)6 {K4 (H2O)4 [V10 O28]} (H2O)4 II and [(CH3)4N]6 [V15 O36 Cl] III, have been synthesized under hydrothermal condition. The relationship between their properties and structures were studied by using FTIR, UV-Vis DRS and flurescence. The FTIR showed that the vibrational frequencies of the group are related to the structure of the materials. In UV-Vis DRS spectra of compound I, there are four characteristic wide peaks at 200, 230, 260 and 350 nm corresponding to O(t) --> V, O(mu) --> Ni, O(mu) --> V charge transfer and phen's pi-pi*, respectively. The fluorescence spectra of clusters have been studies. Finally, the quantum chemistry calculation was performed by Gaussian 98 program to explain the structure characteristic of compound I.

[Spectral study of two Bi (III) contained heteropolymate compounds].

Two Bi (III) contained heteropolymate compounds Cos [Bi2 Co2 W20 O70 (H2O)6] x 44H2O (I)and Na3 H2 [Ce3 (H2O)18 Bi2 W22 O76] x 23H2O (II) have been synthesized under hydrothermal condition. The relationship between their properties and structures was studied by using FTIR, NIR FT-Raman, and UV-Vis DRS etc. The characteristic vibrational frequencies nu(as) (M = O(d)) and nu(s) (M-O(b)-M) is related to the structure of the materials. Nu(as) (M-O(b)-M) is demonstrated to explain why the the oxidative ability becomes stronger when W atoms are substituted by Co atoms. In UV-Vis DRS spectra of compound I and II, there are two characteristic peaks at 254, 319 nm and 220, 310 nm coresponding O(d) --> W and to O(b), c --> W charge transfer, respectively. The wide and weak absorption band of compound I at 529 nm can be assigned as Co2+ d-d transfer. Finally, quantum chemistry calculation of compound I was performed to explain the structure characteristic.

[Spectral study of two compounds of molybdate salt with beta-[Mo8O26] anion].

Two compounds of organic molybdate-alkali salt: [H(4,4'-bipy)]2[K2Mo8O26](I) and H3 [Na Mo8 O26] (4,4'-bipy)5 (H2O)4 (II), with beta-[Mo8O26]4- anion, were synthesized. The relationship between their properties and structures was studied by using FTIR, Raman, NIR-Vis and fluorescence etc. They possess isolating beta-[Mo8O26]4- anion, whose terminal O atoms combine with alkali. The FTIR and Raman spectra showed that the vibrational frequencies of the group are related to the structure of the materials. In UV-Vis spectra of compound (I) and (II), there is a characteristic wide peak at 280-300 nm. The fluorescence spectra of compound (I) and (II) were studied, which showed that the wide emission peak is from 450 to 650 nm and excited by 350 nm for compound (I), and the emission peak is from 400 to 550 nm and excited by 325 nm for compound (II). For compound (I), the intensity of emission becomes stronger with decreasing of temperature, and so does the fluorescence lifetime.

[Spectral study of some polyoxovanadium borates].

Four novel polyoxovanadium borates with [(VO)12O6B18O42], namely (enH2)6 H3 [(VO)12O6B18O42].13H2O(1), [Ni (en)2]6 H3 [(VO)12 O6B18O42].8H2O(2), [Cu(en)2]5 H3 [(VO)12 O6B18 O42] [B(OH)3]2. 16H20(3) and(enH2)4 Na4H3 [(VO)12 O6B18O42].8H2O(4), were synthesized. The relationship between their properties and structures were studied by using FTIR, UV-Vis DRS and fluorescence etc. Among these compounds, compound (1) possesses isolated [(VO)12O6B18O42] cage, there is a ring of B18O42 sandwiched between two vanadium-oxygen clusters V6O18 by eighteen B--(micro3--O)--V bonds, while compound (2) is rather six [Ni(en)2], each connected with the B18O42 ring by two Ni--(micro3--O)--B. In compounds (3) and (4), the anion clusters [(VO)12 O6B18O42]13- are connected with [Cu(en)2]2+ and Na+ , respectively. Thus, the compounds (3) and (4) are extended to an infinite two-dimensional network structure, respectively. These characteristic vibrational frequencies of polyoxovanadium borates are related to the structures of these compounds. In UV/Vis DRS spectra, there are two characteristic peaks of polyoxometalates at 205 and 260 nm, respectively. The fluorescence spectra of these four compounds have been studied, and they have emission peaks at 415 nm excited by 310 nm which are caused by Omicro-->Mo. The fluorescence lifetimes of these compounds have been studied.

Barium divanadium(V) tellurite(IV).

A new three-dimensional bimetallic tellurite, BaV2TeO8, was synthesized by the hydrothermal reaction of Ba(OH)2, TeO2 and V2O5, and characterized by single-crystal X-ray diffraction. The three-dimensional framework is built up from anionic [V2TeO8]n(2n-) layers parallel to (101) and connected via Ba-O bonds. The anionic layers are formed by three types of polyhedra, namely VO5 tetragonal pyramids, VO(4) tetrahedra and TeO(4+2) 'folded square' polyhedra.