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1.
Biochem Biophys Res Commun ; 579: 40-46, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34583194

RESUMO

Protein tyrosine phosphatase 1B (PTP1B) is a member of the phosphotyrosine phosphatase family and plays an important role in the signal transduction of diabetes. Inhibition of PTP1B activity can increase insulin sensitivity and reduce blood sugar levels. Therefore, it is urgent to find compounds with novel structures that can inhibit PTP1B. This study designed imidazolidine-2,4-dione derivatives through the computer-aided drug design (CADD) strategy, and the Comp#10 showed outstanding inhibitory ability. (IC50 = 2.07 µM) and selectivity. The inhibitory mechanism at molecular level of Comp#10 on PTP1B was studied by molecular dynamics simulation. The results show that the catalytic region of PTP1B protein is more stable, which makes the catalytic sites unsuitable for exposure. Interestingly, the most obvious changes in the interaction between residues in the P-loop region (such as: His214, Cys215, and Ser216). In short, this study reported for the first time that imidazolidine-2,4-dione derivatives as novel PTP1B inhibitors had good inhibitory activity and selectivity, providing new ideas for the development of small molecule PTP1B inhibitors.

2.
J Org Chem ; 86(18): 12831-12839, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34477382

RESUMO

(+)- and (-)-talaromyoxaones A and B (1 and 2, respectively), two new oxaphenalenone derivatives with a hemiacetal frame and an unprecedented spirolactone frame of a 2'H,3H,4'H-spiro[isobenzofuran-1,3'-pyran]-3-one unit that show biosynthetic enantiodivergence, and two new oxaphenalenone analogues (±)-11-apopyrenulin (3) and (+)- or (-)-abeopyrenulin (4) were isolated from the marine-derived fungus Talaromyces purpureogenus SCSIO 41517. Their structures were elucidated by spectroscopic analysis, single-crystal X-ray diffraction, and quantum chemical calculations of ECD spectra. Compounds 1 and 2 showed selective inhibitory activity against phosphatases SHP1, SHP2, and MEG2 with IC50 values of 1.3-3.4 µM, and the potential modes of action for 1 were investigated by a preliminary molecular docking study.


Assuntos
Talaromyces , Simulação de Acoplamento Molecular , Monoéster Fosfórico Hidrolases , Espironolactona
3.
Microb Cell Fact ; 20(1): 42, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33579268

RESUMO

BACKGROUND: The co-culture strategy which mimics natural ecology by constructing an artificial microbial community is a useful tool to activate the biosynthetic gene clusters to generate new metabolites. However, the conventional method to study the co-culture is to isolate and purify compounds separated by HPLC, which is inefficient and time-consuming. Furthermore, the overall changes in the metabolite profile cannot be well characterized. RESULTS: A new approach which integrates computational programs, MS-DIAL, MS-FINDER and web-based tools including GNPS and MetaboAnalyst, was developed to analyze and identify the metabolites of the co-culture of Aspergillus sydowii and Bacillus subtilis. A total of 25 newly biosynthesized metabolites were detected only in co-culture. The structures of the newly synthesized metabolites were elucidated, four of which were identified as novel compounds by the new approach. The accuracy of the new approach was confirmed by purification and NMR data analysis of 7 newly biosynthesized metabolites. The bioassay of newly synthesized metabolites showed that four of the compounds exhibited different degrees of PTP1b inhibitory activity, and compound N2 had the strongest inhibition activity with an IC50 value of 7.967 µM. CONCLUSIONS: Co-culture led to global changes of the metabolite profile and is an effective way to induce the biosynthesis of novel natural products. The new approach in this study is one of the effective and relatively accurate methods to characterize the changes of metabolite profiles and to identify novel compounds in co-culture systems.


Assuntos
Aspergillus/crescimento & desenvolvimento , Bacillus subtilis/crescimento & desenvolvimento , Metabolismo Secundário , Técnicas de Cocultura
4.
Mol Divers ; 25(3): 1873-1887, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33392964

RESUMO

The E69K mutation is one of the most frequent protein tyrosine phosphatase-2 (SHP2) mutations in leukemia, and it can cause the increase in the protein activity. Recent studies have shown that the E69K mutation was fairly sensitive to the allosteric inhibitor of SHP2 (SHP099). However, the molecular mechanism of the allosteric drug SHP099 inhibiting SHP2E69K remains unclear. Thus, the molecular dynamic simulations and the post-dynamics analyses (RMSF, PCA, DCCM, RIN and the binding free energies) for SHP2WT, SHP2WT-SHP099, SHP2E69K and SHP2E69K-SHP099 were carried out, respectively. Owing to the strong binding affinity of SHP099 to residues Thr219 and Arg220, the flexibility of linker region (residues Val209-Arg231) was reduced. Moreover, the presence of SHP099 kept the autoinhibition state of the SHP2 protein through enhancing the interactions between the linker region and Q loop in PTP domain, such as Thr219/Val490, Thr219/Asn491, Arg220/Ile488 and Leu254/Asn491. In addition, it was found that the residues (Thr219, Arg220, Leu254 and Asn491) might be the key residues responsible for the conformational changes of protein. Overall, this study may provide an important basis for understanding how the SHP099 effectively inhibited the SHP2E69K activity at the molecular level.

5.
J Mol Graph Model ; 103: 107807, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33338846

RESUMO

Abnormal activation of Ras/MAPK signaling pathway could trigger excessive cell division. Src-homology 2 (SH2) domain-containing protein tyrosine phosphatase (SHP2) could promote Ras/MAPK activation by integrating growth factor signals. Thus, SHP2 inhibitors had become a hot topic in the treatment of cancer. SHP2F285S, mutation in SHP2, was detected in leukemia variants. The compound 2 (3-benzyl-8-chloro-2-hydroxy-4H-benzo[4,5]thiazolo[3,2-a]pyrimidin-4-one) had been reported that it was a potent allosteric inhibitor of both SHP2 wild type (SHP2WT) and the F285S mutant (SHP2F285S). However, the mechanism of inhibition remained to be further discovered. Herein, molecular docking and molecular dynamic (MD) simulation were performed to explain the inhibition mechanism of compound 2 on SHP2WT and SHP2F285S. Overall, the molecular docking analysis revealed that compound 2 maintained the "close" structure of SHP2 protein probably by locking the C-SH2 and PTP domain. Next, post-analysis demonstrated that compound 2 might make TYR66-GLU76 of D'E-loop in N-SH2 and GLU258-LYS266 of B'C-loop, HIS458-ARG465 of P-loop, VAL497-THR507 of Q-loop in PTP domain regions tightly connect and much easier maintain "self-inhibited" conformation of SHP2F285S-compound2 than that of SHP2WT-compound2. Importantly, GLU76 of D'E-loop could play a vital role in inhibition of SHP2WT-compound2 and SHP2F285S-compound2. This work provided a reliable clue to develop novel inhibitors for leukemia related to SHP2F285S.


Assuntos
Simulação de Dinâmica Molecular , Proteína Tirosina Fosfatase não Receptora Tipo 11 , Conformação Molecular , Simulação de Acoplamento Molecular , Mutação , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo
6.
Bioorg Chem ; 107: 104571, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33373758

RESUMO

Nine new xanthone-type and anthraquinone-type mycotoxins including austocystins J-N (1-5), 7-chloro versicolorin A (6), 3'-hydroxy-8-O-methyl versicolorin B (7), 8-O-methyl versiconol (8) and 2',3'-dihydroxy versiconol (9), together with 17 known analogues (10-26) were isolated from an extract of the deep-sea-derived fungus Aspergillus puniceus SCSIO z021. Their structures were elucidated by detailed analysis of spectroscopic data, and their absolute configurations were further determined by quantum chemical calculations of ECD spectra or comparison of the experimental ECD spectra. Eleven hydrogenated austocystins were synthesized from 1-2, 10-15 and 17 by catalytic hydrogenation for bioactivities evaluation. Totally, 18 of the all 37 compounds showed strong toxicity against brine shrimps or Vero cell, and the toxicity of 8-O-methyldemethylsterigmatocystin (18) (LC50 = 0.020 µM) against brine shrimps was higher than those of three positive controls. In addition, 22 of the isolated compounds also exhibited significant inhibitory activity against seven different protein tyrosine phosphatases (PTPs), among them austocystin H (15) and methyl-averantin (24) were the most potent inhibitors with IC50 values of 0.20-3.0 µM. Their structure-bioactivity relationship was also discussed.


Assuntos
Aspergillus/metabolismo , Micotoxinas/química , Proteínas Tirosina Fosfatases/antagonistas & inibidores , Água do Mar/microbiologia , Animais , Artemia/crescimento & desenvolvimento , Aspergillus/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Dicroísmo Circular , Conformação Molecular , Micotoxinas/metabolismo , Micotoxinas/farmacologia , Óvulo/efeitos dos fármacos , Óvulo/crescimento & desenvolvimento , Isoformas de Proteínas/antagonistas & inibidores , Isoformas de Proteínas/metabolismo , Proteínas Tirosina Fosfatases/metabolismo , Relação Estrutura-Atividade , Células Vero
7.
Bioorg Chem ; 105: 104391, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33113413

RESUMO

PTPN11 (coding the gene of SHP2), a classic non-receptor protein tyrosine phosphatase, is implicated in multiple cell signaling pathway. Abnormal activation of SHP2 has been shown to contribute to a variety of human diseases, including Juvenile myelomonocytic leukemia (JMML), Noonan syndrome and tumors. Thus, the SHP2 inhibitors have important therapeutic value. Here, based on the compound PubChem CID 8,478,960 (IC50 = 45.01 µM), a series of thiophene [2,3-d] pyrimidine derivatives (IC50 = 0.4-37.87 µM) were discovered as novel and efficient inhibitors of SHP2 through powerful "core hopping" and CDOCKER technology. Furthermore, the SHP2-PTP phosphatase activity assay indicated that Comp#5 (IC50 = 0.4 µM) was the most active SHP2 inhibitor. Subsequently, the effects of Comp#5 on the structure and function of SHP2 were investigated through molecular dynamics (MD) simulation and post-kinetic analysis. The result indicated that Comp#5 enhanced the interaction of residues THR357, ARG362, LYS366, PRO424, CYS459, SER460, ALA461, ILE463, ARG465, THR507 and GLN510 with the surrounding residues, improving the stability of the catalytic active region and the entrance of catalytic active region. In particular, the Comp#5 conjugated with residue ARG362, elevating the efficient and selectivity of SHP2 protein. The study here may pave the way for discovering the novel SHP2 inhibitors for suffering cancer patients.


Assuntos
Desenho de Fármacos , Inibidores Enzimáticos/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 11/antagonistas & inibidores , Pirimidinas/farmacologia , Tiofenos/farmacologia , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Modelos Moleculares , Estrutura Molecular , Análise de Componente Principal , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Pirimidinas/síntese química , Pirimidinas/química , Relação Estrutura-Atividade , Tiofenos/síntese química , Tiofenos/química
8.
Org Lett ; 22(16): 6330-6333, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32806192

RESUMO

Three novel andrastin-type meroterpenoids, penicimeroterpenoids A-C (1-3), possessing two unprecedented skeletons consisting of fused 6/5/6/6/7 and 6/5/6/6/4 polycyclic systems, were obtained from the marine-derived fungus Penicillium sp. SCSIO 41512. Their structures were determined by spectroscopic methods, and the absolute configurations were further determined by single-crystal X-ray diffraction analysis for 1 and quantum chemical calculations of ECD spectra for 2 and 3, respectively. A plausible biosynthetic pathway for 1-3 was proposed.


Assuntos
Penicillium/química , Terpenos/química , Fenômenos Bioquímicos , Cristalografia por Raios X , Estrutura Molecular , Terpenos/isolamento & purificação
9.
RNA Biol ; 17(10): 1508-1519, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32507001

RESUMO

At present, the functional recovery after nerve injury is not satisfactory in clinical practice. The aim of this study was to explore the molecular mechanism of miR-21 promoting Schwann cells (SC) proliferation and axon regeneration after peripheral nerve injury, providing a theoretical basis for injured nerve repair. Nerve injury models were constructed to determine the expression of miR-21 in the injured nerve by Quantitative Real-Time PCR (qRT-PCR). After miR-21 over-expression SC (mimic-miR-21) group, control SC (control-miR-21) group and blank SC (RSC96) group were constructed, SC proliferation was determined by CCK-8, cell cycle was analysed by flow cytometry, dorsal root ganglion neuron (DRGn) axon regeneration was observed after DRGn was cultured with SCs for 7 days, the expressions of TGFßI, TIMP3, EPHA4 as well as apoptosis-related proteins caspase-3 and caspase-9 were detected by qRT-PCR and Western blot in the three groups, respectively. Target genes were confirmed by dual-luciferase reporter gene assay. The expressions of TGFßI, TIMP3 and EPHA4 were assessed by immunofluorescence in vivo. qRT-PCR indicated that miR-21 expression was significantly higher in the model group than in the sham operation and blank groups. SC proliferation index (PI) was significantly higher, the apoptosis rate was significantly lower, the axon was significantly longer, and mRNA and protein expressions of TGFßI, TIMP3, EPHA4 as well as apoptosis-related proteins caspase-3 and caspase-9 were significantly lower in the mimic-miR-21 group than in the control-miR-21 and RSC96 groups. The double luciferase assay confirmed that TGFßI, TIMP3 and EPHA4 were potential target genes of miR-21. In vivo immunofluorescence also indicated that expressions of TGFßI, TIMP3, EPHA4 were lower in the mimic-miR-21 group than in the control-miR-21 and RSC96 groups. We conclude that during injured peripheral nerve repair, miRNA-21 plays an important role in promoting SC proliferation and axon regeneration by regulating TGFßI, TIMP3 and EPHA4 target genes.


Assuntos
Axônios/fisiologia , MicroRNAs/genética , Regeneração Nervosa , Neurogênese/genética , Traumatismos dos Nervos Periféricos/genética , Células de Schwann/fisiologia , Animais , Apoptose/genética , Biomarcadores , Proliferação de Células , Células Cultivadas , Modelos Animais de Doenças , Gânglios Espinais/citologia , Gânglios Espinais/metabolismo , Expressão Gênica , Regulação da Expressão Gênica , Genes Reporter , Masculino , Neurônios/fisiologia , Traumatismos dos Nervos Periféricos/metabolismo , Traumatismos dos Nervos Periféricos/patologia , Ratos , Transfecção
10.
J Biomol Struct Dyn ; 38(13): 3814-3824, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31490104

RESUMO

Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of insulin signaling pathway, and more and more studies have shown that it is a potential target for the treatment of type 2 diabetes mellitus (T2DM). In this study, 17 new 4-thiazolinone derivatives were designed and synthesized as novel PTP1B inhibitors, and ADMET prediction confirmed that these compounds were to be drug-like. In vitro enzyme activity experiments were performed on these compounds, and it was found that a plurality of compounds had good inhibitory activity and high selectivity against PTP1B protein. Among them, compound 7p exhibited the best inhibitory activity with an IC50 of 0.92 µM. The binding mode of compound 7p and PTP1B protein was explored, revealing the reason for its high efficiency. In addition, molecular dynamics simulations for the PTP1BWT and PTP1Bcomp#7p systems revealed the effects of compound 7p on PTP1B protein at the molecular level. In summary, the study reported for the first time that 4-thiazolinone derivatives as a novel PTP1B inhibitor had good inhibitory activity and selectivity for the treatment of T2DM, providing more options for the development of PTP1B inhibitors. AbbreviationsBBBblood-brain barrierCDC25Bcell division cycle 25 homolog BCYP2D6Cytochrome P450 2D6 bindingDCCMdynamic cross-correlation mapDSDiscovery StudioH bondhydrogen bondHIAhuman intestinal absorptionLARleukocyte antigen-related phosphataseMDmolecular dynamicsMEG-2maternal-effect germ-cell defective 2MM-PBSAmolecular mechanics Poisson Boltzmann surface area)PCAprincipal component analysisPDBProtein Data BankpNPPp-nitrophenyl phosphatePPBplasma protein bindingPTP1Bprotein tyrosine phosphotase 1BRMSDroot mean square deviationRMSFroot mean square fluctuationSHP-1src homologous phosphatase-1SHP-2src homologous phosphatase-2SPCsingle-point chargeTCPTPT cell protein tyrosine phosphataseT2DMType 2 diabetes mellitusVDWvan der WaalsCommunicated by Ramaswamy H. Sarma.


Assuntos
Inibidores Enzimáticos , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Diabetes Mellitus Tipo 2 , Inibidores Enzimáticos/farmacologia , Humanos , Insulina , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Relação Estrutura-Atividade
11.
J Biomol Struct Dyn ; 38(15): 4432-4448, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31625456

RESUMO

Owing to their unique functions in regulating the synapse activity of protein tyrosine phosphatases delta (PTPδ) that has drawn special attention for developing drugs to autism spectrum disorders (ASDs). In this study, the PTPδ pharmacophore was first established by the structure-based pharmacophore method. Subsequently, 10 compounds contented Lipinski's rule of five was acquired by the virtual screening of the PTPδ pharmacophore against ZINC and PubChem databases. Then, the 10 identified molecules were discovered that had better binding affinity than a known PTPδ inhibitors compound SCHEMBL16375396. Two compounds SCHEMBL16375408 and ZINC19796658 with high binding score, low toxicity were gained. They were observed by docking analysis and molecular dynamics simulations that the novel potential inhibitors not only possessed the same function as SCHEMBL16375396 did in inhibiting PTPδ, but also had more favorable conformation to bind with the catalytic active regions. This study provides a new method for identify PTPδ inhibitor for the treatment of ASDs disease.Communicated by Ramaswamy H. Sarma.


Assuntos
Simulação de Dinâmica Molecular , Relação Quantitativa Estrutura-Atividade , Domínio Catalítico , Simulação de Acoplamento Molecular , Proteínas Tirosina Fosfatases
12.
J Biomol Struct Dyn ; 38(14): 4232-4245, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31588870

RESUMO

Owing to its negative regulatory role in insulin signaling, protein tyrosine phosphatase of leukocyte antigen-related protein (PTP-LAR) was widely thought as a potential drug target for diabetes. Now, it was urgent to search for potential LAR inhibitors targeting diabetes. Initially, the pharmacophore models of LAR inhibitors were established with the application of the HypoGen module. The cost analysis, test set validation, as well as Fischer's test was used to verify the efficiency of pharmacophore model. Then, the best pharmacophore model (Hypo-1-LAR) was applied for the virtual screening of the ZINC database. And 30 compounds met the Lipinski's rule of five. Among them, 10 compounds with better binding affinity than the known LAR inhibitor (BDBM50296375) were discovered by docking studies. Finally, molecular dynamics simulations and post-analysis experiments (RMSD, RMSF, PCA, DCCM and RIN) were conducted to explore the effect of ligands (ZINC97018474 and Compound 1) on LAR and preliminary understand why ZINC97018474 had better inhibitory activity than Compound 1 (BDBM50296375). Communicated by Ramaswamy H. Sarma.


Assuntos
Simulação de Dinâmica Molecular , Relação Quantitativa Estrutura-Atividade , Leucócitos , Ligantes , Simulação de Acoplamento Molecular
13.
J Biomol Struct Dyn ; 38(18): 5338-5348, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31787068

RESUMO

The overexpression of PTP-LAR could cause the insulin resistance, so PTP-LAR might be a promising target for treating diabetes. In this study, we applied the computer modeling methods with fragment replace approach to screen the fragment database by targeting PTP domain and site B with the aim to discover potent and selective PTP-LAR inhibitors. A series of novel 4-thiazolidone derivatives were gained. The results of their ADMET predictions indicated that these new compounds might become drug candidates. The series of these derivatives were synthesized. Subsequently, their PTP-LAR inhibitory activities were assayed. The compound7d showed highly selectivity for PTP-LAR (10.41 µM) over its close homolog PTP1B (IC50=44.40 µM), SHP2 (IC50>122.81 µM) and CDC25B (IC50>122.81 µM) and docking and molecular dynamics simulation were applied to propose the most likely binding mode of compound7d with PTP-LAR. Thus, our findings reported here may pave a way for discovering potential selective PTP-LAR inhibitors.AbbreviationsPTP-LARHuman leukocyte common antigen-relatedPTPProtein Tyrosine PhosphataseIRinsulin receptorPTP1BProtein tyrosine phosphatase-1BLRPLung resistance proteinADMETabsorption, distribution, metabolism, excretion, toxicityPPBplasma protein bindingBBBblood brain barrier penetrationCYP450cytochrome P450HIAhuman intestinal absorptionTLCthin-layer chromatographyUVUltra VioletNMRnuclear magnetic resonanceTMStetramethylsilaneMSmass spectrometryANManisotropic network modePDBProtein Data BankDMFN,N-DimethylformamidepNPPpara-nitrophenyl phosphateDTTdithiothreitolMDmolecular dynamicRMSDroot-mean-square deviationRMSFroot-mean-square fluctuationSPCsingle-point chargePMEParticle Mesh EwaldMM-PBSAmolecular mechanics Poisson Boltzmann surface areaH bond, hydrogen bondVDWVan der WaalsCommunicated by Ramaswamy H. Sarma.


Assuntos
Diabetes Mellitus , Inibidores Enzimáticos , Antígenos Comuns de Leucócito , Simulação por Computador , Diabetes Mellitus/tratamento farmacológico , Antígenos HLA , Humanos
14.
Comput Biol Chem ; 83: 107123, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31561070

RESUMO

The low molecular weight protein tyrosine phosphatase (LMW-PTP) could regulate many signaling pathways, and it had drawn attention as a potential target for cancer. As previous report has indicated that the aplidin could inhibit the LMW-PTP, and thus, the relevant cancer caused by the abnormal regulation of the LMW-PTP could be remission. However, the molecular mechanism of inhibition of the LMW-PTP by the aplidin had not been fully understood. In this study, various computational approaches, namely molecular docking, MDs and post-dynamic analyses were utilized to explore the effect of the aplidin on the LMW-PTP. The results suggested that the intramolecular interactions of the residues in the two sides of the active site (Ser43-Ala55 and Pro121-Asn134) and the P-loop region (Leu13-Ser19) in the LMW-PTP was disturbed owing to the aplidin, meanwhile, the π-π interaction between Tyr131 and Tyr132 might be broken. The Asn15 might be the key residue to break the residues interactions. In a word, this study may provide more information for understanding the effect of inhibition of the aplidin on the LMW-PTP.


Assuntos
Depsipeptídeos/farmacologia , Inibidores Enzimáticos/farmacologia , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Proteínas Tirosina Fosfatases/antagonistas & inibidores , Domínio Catalítico/efeitos dos fármacos , Depsipeptídeos/química , Inibidores Enzimáticos/química , Humanos , Conformação Molecular , Peso Molecular , Proteínas Tirosina Fosfatases/química , Proteínas Tirosina Fosfatases/metabolismo
15.
Acta Crystallogr E Crystallogr Commun ; 73(Pt 11): 1790-1792, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29152375

RESUMO

In the title compound, C29H25FN2O4, the mean planes of the two indole ring systems (r.m.s. deviations = 0.1392 and 0.0115 Å) are approximately perpendicular to one another, subtending a dihedral angle of 86.0 (5)°; the benzene ring is twisted with respect to the mean planes of the two indole ring systems by 83.3 (2) and 88.1 (4)°, respectively. In the crystal, pairs of N-H⋯O hydrogen bonds link the mol-ecules into centrosymmetric dimers, which are further linked by N-H⋯O hydrogen bonds into supra-molecular chains propagating along the [101] direction.

16.
Acta Crystallogr C Struct Chem ; 72(Pt 11): 895-900, 2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-27811432

RESUMO

The self-assembly of coordination polymers and the crystal engineering of metal-organic coordination frameworks have attracted great interest, but it is still a challenge to predict and control the compositions and structures of the complexes. Employing multidentate organic ligands and suitable metal ions to construct inorganic-organic hybrid materials through metal-ligand coordination and hydrogen-bonding interactions has become a major strategy. Recently, imidazole-containing multidentate ligands that contain an aromatic core have received much attention. A new three-dimensional MnII coordination polymer based on 1,3,5-tris[(1H-imidazol-1-yl)methyl]benzene, namely poly[(ethane-1,2-diol-κO)(µ-sulfato-κ2O:O'){µ3-1,3,5-tris[(1H-imidazol-1-yl)methyl]benzene-κ3N:N':N''}manganese(II)], [Mn(SO4)(C18H18N6)(C2H6O2)]n, was synthesized and characterized by elemental analysis, IR spectroscopy and single-crystal X-ray diffraction. Crystal structural analysis shows that there are two kinds of crystallographically independent MnII centres, each lying on a centrosymmetric position and having a similar six-coordinated octahedral structure. One is coordinated by four N atoms from four 1,3,5-tris[(1H-imidazol-1-yl)methyl]benzene (timb) ligands and two O atoms from two different bridging sulfate anions. The second is surrounded by two timb N atoms and four O atoms, two from sulfate anions and two from two ethane-1,2-diol ligands. The tripodal timb ligand bridges neighbouring MnII centres to generate a two-dimensional layered structure running parallel to the ab plane. Adjacent layers are further bridged by sulfate anions, resulting in a three-dimensional structure with 3,4,6-c topology. Thermogravimetric analysis of the title polymer shows that it is stable up to 533 K. The first weight loss between 533 and 573 K corresponds to the release of coordinated ethane-1,2-diol molecules, and further decomposition occurred at 648 K.

17.
Int J Syst Evol Microbiol ; 66(12): 5129-5133, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27613380

RESUMO

An alkalitolerant actinomycete strain, designated EGI 80674T, was isolated from a rhizosphere soil of Halocnermumstrobilaceum (Pall.) Bieb in Xinjiang, north-west China and subjected to a taxonomic characterization using a polyphasic approach. Strain EGI 80674T formed white aerial hyphae with long spore chains. Whole-cell hydrolysates of the isolate contained meso-diaminopimelic acid as the diagnostic diamino acid with no diagnostic sugars. The major fatty acids identified were iso-C16 : 0, anteiso-C17 : 0 and 10-methyl-C18 : 0TBSA. The predominant menaquinones detected were MK-10(H8) and MK-10(H6). The G+C content of the genomic DNA of strain EGI 80674T was 70.9 mol%. Strain EGI 80674T showed the highest 16S rRNA gene sequence similarity (97.24 %) to Nocardiopsis nikkonensis NBRC 102170T. The DNA-DNA relatedness value of strain EGI 80674T and N. nikkonensis NBRC 102170T was 18.4±1.3 %. Phenotypical, chemotaxonomic and phylogenetic characteristics and DNA-DNA hybridization data suggest that strain EGI 80674T represents a novel species of the genus Nocardiopsis, for which the name Nocardiopsis rhizosphaerae sp. nov. is proposed. The type strain is EGI 80674T (=CGMCC 4.7228T=KCTC 39673T).


Assuntos
Actinobacteria/classificação , Chenopodiaceae/microbiologia , Filogenia , Rizosfera , Microbiologia do Solo , Actinobacteria/genética , Actinobacteria/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , Hibridização de Ácido Nucleico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/química
18.
Bioorg Med Chem Lett ; 26(21): 5328-5333, 2016 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-27671500

RESUMO

With the aim of finding more potential inhibitors against NADH-fumarate reductase (specific target for treating helminthiasis and cancer) from natural resources, Talaromyces wortmannii was treated with the epigenome regulatory agent suberoylanilide hydroxamic acid, which resulted in the isolation of four new wortmannilactones derivatives (wortmannilactones I-L, 1-4). The structures of these new compounds were elucidated based on IR, HRESIMS and NMR spectroscopic data analyses. These four new compounds showed potent inhibitory activity against NADH-fumarate reductase with the IC50 values ranging from 0.84 to 1.35µM.


Assuntos
Ácidos Hidroxâmicos/farmacologia , Macrolídeos/farmacologia , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/antagonistas & inibidores , Talaromyces/química , Meios de Cultura , Macrolídeos/química , Estrutura Molecular , Análise Espectral/métodos , Vorinostat
19.
Int J Syst Evol Microbiol ; 66(10): 4071-4076, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27412719

RESUMO

An alkaliphilic and halophilic actinomycete strain, designated EGI 80537T, was isolated from a saline-alkali soil sample of Xinjiang, north-west China and subjected to a taxonomic characterization using a polyphasic approach. Strain EGI 80537T formed reticulate long aerial hyphae. Whole-cell hydrolysates of the isolate contained meso-diaminopimelic acid as the cell-wall diamino acid and mannose as the diagnostic sugar. The major fatty acids identified were iso-C16 : 0, anteiso-C17 : 0 and 10-methyl-C18 : 0 (TBSA). The predominant menaquinones detected were MK-10(H8) and MK-10(H6). The G+C content of the genomic DNA of strain EGI 80537T was 67.6 mol%. Strain EGI 80537T showed the highest 16S rRNA gene sequence similarity to Allosalinactinospora lopnorensis CA15-2T (96.7 %). Phylogenetic analysis showed that strain EGI 80537T clustered with the members of the family Nocardiopsaceae. Based on phenotypic, chemotaxonomic and phylogenetic characteristics, strain EGI 80537T represents a novel species of a new genus in the family Nocardiopsaceae, for which the name Lipingzhangella halophila gen. nov., sp. nov. is proposed. The type strain of the type species is EGI 80537T(=CGMCC 4.7224T= DSM 102030T).


Assuntos
Actinomycetales/classificação , Filogenia , Microbiologia do Solo , Actinomycetales/genética , Actinomycetales/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/química
20.
Int J Syst Evol Microbiol ; 66(5): 2058-2063, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26920762

RESUMO

An alkaliphilic, filamentous actinomycete, designated EGI 80629T, was isolated from a soil sample of Xinjiang, north-west China. Strain EGI 80629T grew at pH 6.0-11.0 (optimum pH 9.0-10.0) and in the presence of 0-13.0 % NaCl (optimum 3.0-5.0 %). The isolate formed fragmented substrate mycelia, and aerial hyphae with short spore chains with rod-like spores. Whole-cell hydrolysates of the isolate contained ll-diaminopimelic acid as the diagnostic diamino acid, and mannose and rhamnose as diagnostic sugars. The major fatty acids identified were iso-C15 : 0, iso-C16 : 0, anteiso-C15 : 0 and iso-C17 : 0. The predominant menaquinone was MK-9(H4), while the polar lipids were diphosphatidylglycerol, phosphatidylglycerol, two phosphatidylinositol mannosides, five unknown phospholipids, three unknown phosphoglycolipids, one unknown glycolipid, four unknown polar lipids and one unknown aminophospholipid. The G+C content of the genomic DNA was 67.3 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain EGI 80629T clustered with the genus Phytoactinopolyspora. The 16S rRNA gene sequence similarity between strain EGI 80629T and Phytoactinopolyspora endophytica EGI 60009T was 96.8 %. Based on morphological, chemotaxonomic and phylogenetic characteristics, strain EGI 80629T represents a novel species of the genus Phytoactinopolyspora, for which the name Phytoactinopolyspora alkaliphila sp. nov. is proposed. The type strain is EGI 80629T ( = CGMCC 4.7225T = KCTC 39701T).


Assuntos
Actinomycetales/classificação , Filogenia , Microbiologia do Solo , Actinomycetales/genética , Actinomycetales/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , Glicolipídeos/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
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