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[PMID]:29185856
[Au] Autor:Moghadam ME; Divsalar A; Zare MS; Gholizadeh R; Mahalleh D; Saghatforosh L; Sanati S
[Ad] Endereço:a Chemistry & Chemical Engineering Research Center of Iran , Tehran , Iran.
[Ti] Título:Anticancer, antibacterial and antifungal activity of new ni (ii) and cu (ii) complexes of imidazole-phenanthroline derivatives.
[So] Source:Nucleosides Nucleotides Nucleic Acids;36(11):667-675, 2017 Nov 02.
[Is] ISSN:1532-2335
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Two new nickel(II) and copper(II) complexes of 2-(Furan-2-yl)-1H-Imidazo[4,5-f][1,10]Phenanthroline (FIP) and 2-(thiophen-2-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (TIP), imidazophen derivatives were synthesized. The structures of the compounds were determined by UV-visible and FT-IR spectroscopic methods and elemental analysis. The biological activities of Ni and Cu complexes, as anticancer agents, were tested against chronic myelogenous leukemia cell line, K562, at micromolar concentration. The MTT studies showed Cc values are 21 and 160 µM for Cu and Ni(II) complexes, respectively; suggesting that Ni (II) complex has Cc almost seven times of that obtained for cisplatin. Biological activity of the Ni(II) and Cu(II) complexes were also assayed against selective microorganisms by disc diffusion method. These results showed that the Cu(II) complex is antifungal agent but Ni(II) complex has antibacterial activity.
[Mh] Termos MeSH primário: Complexos de Coordenação/química
Complexos de Coordenação/farmacologia
Cobre/química
Imidazóis/química
Níquel/química
Fenantrolinas/química
[Mh] Termos MeSH secundário: Antibacterianos/síntese química
Antibacterianos/química
Antibacterianos/farmacologia
Antifúngicos/síntese química
Antifúngicos/química
Antifúngicos/farmacologia
Antineoplásicos/síntese química
Antineoplásicos/química
Antineoplásicos/farmacologia
Proliferação Celular/efeitos dos fármacos
Complexos de Coordenação/síntese química
Seres Humanos
Células K562
Testes de Sensibilidade Microbiana
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Antifungal Agents); 0 (Antineoplastic Agents); 0 (Coordination Complexes); 0 (Imidazoles); 0 (Phenanthrolines); 789U1901C5 (Copper); 7OV03QG267 (Nickel)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180101
[Lr] Data última revisão:
180101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171130
[St] Status:MEDLINE
[do] DOI:10.1080/15257770.2017.1388393


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[PMID]:28780455
[Au] Autor:Nath M; Mridula; Kumari R
[Ad] Endereço:Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee 247667, India.. Electronic address: malanfcy@iitr.ernet.in.
[Ti] Título:Microwave-assisted synthesis of mixed ligands organotin(IV) complexes of 1,10-phenanthroline and l-proline: Physicochemical characterization, DFT calculations, chemotherapeutic potential validation by in vitro DNA binding and nuclease activity.
[So] Source:J Photochem Photobiol B;174:182-194, 2017 Sep.
[Is] ISSN:1873-2682
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Diorganotin(IV) and triphenyltin(IV) derivatives of L-proline (HPro) having general formula R Sn(Pro) (R=n-Bu (1), Ph (2)) and Ph Sn(Pro) (3), respectively, and the mixed ligands di-/triorganotin(IV) derivatives of L-proline and 1,10-phenanthroline (phen) with general formula [R Sn(Pro)(Phen)Cl] and [R Sn(Pro)(Phen)] (where R=Me (4 and 7), n-Bu (5 and 8), Ph (6 and 9)), respectively, have been synthesized by microwave-assisted method and characterized by elemental analysis, IR, NMR ( H, C and Sn) and DART-mass spectral studies. The results suggest bicapped tetrahedron or a skew trapezoidal-bipyramid geometry for R Sn(Pro) , a distorted tetrahedral geometry for Ph Sn(Pro) and a distorted octahedral geometry for [R Sn(Pro)(Phen)Cl] and [Ph Sn(Pro)(Phen)] around the Sn atom, and the same has been validated by density functional theory calculations (DFT). In vitro DNA binding studies of 1-9 have been investigated by UV-Vis, fluorescence and circular dichroism titrations, viscosity and DNA melting experiments. The observed hypochromic shift in UV-Vis and fluorescence studies evidenced a partial intercalative mode of binding of complexes to CT-DNA. The binding affinity and quenching ability have been quantified in terms of intrinsic binding constant (K ) and Stern-Volmer quenching constant (Ksv). The determined values suggest that di- and triorganotin(IV) derivatives of L-proline possess lesser affinity to bind with CT-DNA in comparison to the mixed ligands di-/triorganotin(IV) derivatives of L-proline and 1,10-phenanthroline. The partial intercalative mode of binding of these complexes with CT DNA has also been supported by a change in the viscosity and melting point of DNA as well as a change in the intensity of positive and negative bands in circular dichroism spectra. The cleavage studies by agarose gel electrophoresis indicate effective cleavage of supercoiled plasmid DNA into its nicked form by all the complexes and even to its linear form in presence of 9.
[Mh] Termos MeSH primário: DNA/metabolismo
Desoxirribonucleases/metabolismo
Micro-Ondas
Compostos Orgânicos de Estanho/química
Compostos Orgânicos de Estanho/metabolismo
Fenantrolinas/química
Prolina/química
[Mh] Termos MeSH secundário: Fenômenos Químicos
Técnicas de Química Sintética
DNA/química
Ligantes
Modelos Moleculares
Conformação Molecular
Desnaturação de Ácido Nucleico
Compostos Orgânicos de Estanho/síntese química
Compostos Orgânicos de Estanho/farmacologia
Teoria Quântica
Temperatura de Transição
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ligands); 0 (Organotin Compounds); 0 (Phenanthrolines); 9007-49-2 (DNA); 9DLQ4CIU6V (Proline); EC 3.1.- (Deoxyribonucleases); W4X6ZO7939 (1,10-phenanthroline)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171012
[Lr] Data última revisão:
171012
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170807
[St] Status:MEDLINE


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[PMID]:28753522
[Au] Autor:Jain S; Khan TA; Patil YP; Pagariya D; Kishore N; Tapryal S; Naik AD; Naik SG
[Ad] Endereço:Department of Chemistry, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandarsindri-305817, NH-8, Jaipur-Ajmer Express way, Ajmer district, Rajasthan, India.
[Ti] Título:Bio-affinity of copper(II) complexes with nitrogen and oxygen donor ligands: Synthesis, structural studies and in vitro DNA and HSA interaction of copper(II) complexes.
[So] Source:J Photochem Photobiol B;174:35-43, 2017 Sep.
[Is] ISSN:1873-2682
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Reported herein the binding affinity between Human Serum Albumin and the DNA binding and cleavage activity of three copper(II) complexes, [Cu(phen)(o-van)ClO ] (1), [Cu(phen)(gly)]ClO (2) and [Cu(L ) (H O) ] (3) wherein 1 and 2 are synthesized with 1,10-phenanthroline (phen) and co-ligands (o-van: o-vanillin; gly: glycine) and 3 with a ligand 2-hydroxy-3-methoxybenzylidene-4H-1,2,4-triazol-4-amine (H L ). Complex 2 crystallizes in monoclinic (P21/n) space group shows square pyramidal geometry. The complex 3 crystallizes in monoclinic (P21/a) space group. All the three complexes exhibit binding affinity towards the transport protein Human Serum albumin (HSA). Quantitative evaluation of the thermodynamics of interaction and the results obtained from fluorescence spectroscopy suggest that metal coordinated glycynate, o-vanillin and perchlorate groups have a major role to play in the binding process, the latter two being stronger in the binding of complex 1. The coordinated water in complex 3 also plays an important role in the binding, which makes binding of complex 3 with HSA stronger than that of complex 2. Experimental results indicate that the binding affinity of the complexes towards CT-DNA is in the order 1>3>2 implying that complex 1 binds stronger than complex 3 and 2.The DNA cleaving activity of all the three complexes was explored in the presence of reactive oxygen compound, H O . All the three complexes have primarily shown the DNA cleaving activity.
[Mh] Termos MeSH primário: Cobre/química
DNA/metabolismo
Nitrogênio/química
Compostos Organometálicos/síntese química
Compostos Organometálicos/metabolismo
Oxigênio/química
Albumina Sérica/metabolismo
[Mh] Termos MeSH secundário: Animais
Benzaldeídos/química
Bovinos
Técnicas de Química Sintética
Clivagem do DNA/efeitos dos fármacos
Seres Humanos
Modelos Moleculares
Conformação Molecular
Compostos Organometálicos/química
Compostos Organometálicos/farmacologia
Fenantrolinas/química
Ligação Proteica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzaldehydes); 0 (Organometallic Compounds); 0 (Phenanthrolines); 0 (Serum Albumin); 008LR748FI (2-vanillin); 789U1901C5 (Copper); 9007-49-2 (DNA); N762921K75 (Nitrogen); S88TT14065 (Oxygen); W4X6ZO7939 (1,10-phenanthroline)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170729
[St] Status:MEDLINE


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[PMID]:28666888
[Au] Autor:Oh J; Kim GD; Kim S; Lee SK
[Ad] Endereço:College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
[Ti] Título:Antofine, a natural phenanthroindolizidine alkaloid, suppresses angiogenesis via regulation of AKT/mTOR and AMPK pathway in endothelial cells and endothelial progenitor cells derived from mouse embryonic stem cells.
[So] Source:Food Chem Toxicol;107(Pt A):201-207, 2017 Sep.
[Is] ISSN:1873-6351
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Although antofine, a natural phenanthroindolizidine alkaloid, exerts potential biological activities, including anticancer effect and anti-angiogenic activity, the underlying mechanisms have not yet been investigated. In the present study, the inhibitory effect of antofine on angiogenesis was determined in cultured mouse embryonic stem (mES)/embryoid body (EB)-derived endothelial cells and vascular endothelial growth factor (VEGF)-induced human umbilical vein endothelial cells (HUVECs). Antofine effectively inhibited VEGF-induced cell migration and tube formation of HUVECs. Antofine also significantly decreased ex vivo microvessel sprouting in cultured mouse aortic rings, and inhibited the vascular formation and platelet/endothelial cell adhesion molecule (PECAM) expression of mES/EB-derived cells in 3-D collagen gel. The underlying mechanism of anti-angiogenic activity of antofine was, in part, associated with the modulation of AKT/mTOR and AMP-activated protein kinase (AMPK) signaling in VEGF-stimulated HUVECs.
[Mh] Termos MeSH primário: Proteínas Quinases Ativadas por AMP/metabolismo
Inibidores da Angiogênese/farmacologia
Células Progenitoras Endoteliais/efeitos dos fármacos
Indóis/farmacologia
Células-Tronco Embrionárias Murinas/efeitos dos fármacos
Neovascularização Patológica/metabolismo
Fenantrolinas/farmacologia
Proteínas Proto-Oncogênicas c-akt/metabolismo
Serina-Treonina Quinases TOR/metabolismo
[Mh] Termos MeSH secundário: Proteínas Quinases Ativadas por AMP/genética
Animais
Proliferação Celular/efeitos dos fármacos
Células Progenitoras Endoteliais/citologia
Células Progenitoras Endoteliais/metabolismo
Seres Humanos
Indolizinas/farmacologia
Camundongos
Células-Tronco Embrionárias Murinas/citologia
Células-Tronco Embrionárias Murinas/metabolismo
Neovascularização Patológica/tratamento farmacológico
Neovascularização Patológica/genética
Neovascularização Patológica/fisiopatologia
Proteínas Proto-Oncogênicas c-akt/genética
Transdução de Sinais/efeitos dos fármacos
Serina-Treonina Quinases TOR/genética
Fator A de Crescimento do Endotélio Vascular/genética
Fator A de Crescimento do Endotélio Vascular/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Angiogenesis Inhibitors); 0 (Indoles); 0 (Indolizines); 0 (Phenanthrolines); 0 (Vascular Endothelial Growth Factor A); 0 (antofine); 0 (phenanthroindolizidine); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 2.7.11.31 (AMP-Activated Protein Kinases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170702
[St] Status:MEDLINE


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[PMID]:28644726
[Au] Autor:M Vidal L; Pimentel E; Cruces MP; Hernández S; Ruiz-Azuara L
[Ad] Endereço:a Departamento de Biología , Instituto Nacional de Investigaciones Nucleares , Ocoyoacac , México.
[Ti] Título:Cytotoxic and genotoxic actions of Casiopeina III-Ea (Cas III-Ea) in somatic and germ cells of Drosophila melanogaster.
[So] Source:J Toxicol Environ Health A;80(6):365-373, 2017.
[Is] ISSN:1528-7394
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Casiopeinas® are a group of newly synthesized drugs designed to treat cancer. These copper (Cu) complexes exhibit cytostatic, cytotoxic, genotoxic, and antineoplastic activities through different mechanisms of action. To evaluate the influence of these compounds, some in vivo studies were performed using predominantly somatic cells. The aim of the present study was to examine the cytotoxic and genotoxic actions of Casiopeina III-Ea (Cas III-Ea) in somatic as well as germ cells of Drosophila melanogaster. For cytotoxicity, the productivity and some morphometric parameters were measured and genotoxicity was assessed by means of the somatic mutation and recombination test assay in the wing. For this purpose, second-instar larvae of the Canton-S strain were treated with different concentrations of Cas III-Ea. The emerged adults were weighed, the area of the wings determined, and the number of trichomes of the region C' counted. The productivity of treated males was measured by a brood method to monitor the influence of Cas III-Ea on spermatozoa, meiotic stage cells, and spermatogonia. For genotoxicity, mwh + /+ flr larvae 48 hr age were chronically treated within the same concentration range. Results indicated that Cas III-Ea at all concentrations tested significantly increased the productivity per couple in Brood III (spermatids) while at 1 mM a marked elevation was noted in the three broods tested. In contrast, the weight and size of individuals as well as the size and number of cells in the wing were decreased significantly. Data suggest that Cas III-Ea is a weak genotoxic but selective mutagen. Failure to obtain a dose-related genotoxic response suggests that one of the preferred mechanisms of action of Cas III-Ea is to induce apoptosis.
[Mh] Termos MeSH primário: Antineoplásicos/toxicidade
Complexos de Coordenação/toxicidade
Fenantrolinas/toxicidade
[Mh] Termos MeSH secundário: Animais
Drosophila melanogaster/efeitos dos fármacos
Feminino
Células Germinativas/efeitos dos fármacos
Masculino
Testes de Mutagenicidade
Asas de Animais/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Coordination Complexes); 0 (Phenanthrolines); 0 (casiopeína III-Ea)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170714
[Lr] Data última revisão:
170714
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170624
[St] Status:MEDLINE
[do] DOI:10.1080/15287394.2017.1326072


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[PMID]:28640600
[Au] Autor:Plapp BV; Savarimuthu BR; Ferraro DJ; Rubach JK; Brown EN; Ramaswamy S
[Ad] Endereço:Department of Biochemistry, The University of Iowa , Iowa City, Iowa 52242, United States.
[Ti] Título:Horse Liver Alcohol Dehydrogenase: Zinc Coordination and Catalysis.
[So] Source:Biochemistry;56(28):3632-3646, 2017 Jul 18.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:During catalysis by liver alcohol dehydrogenase (ADH), a water bound to the catalytic zinc is replaced by the oxygen of the substrates. The mechanism might involve a pentacoordinated zinc or a double-displacement reaction with participation by a nearby glutamate residue, as suggested by studies of human ADH3, yeast ADH1, and some other tetrameric ADHs. Zinc coordination and participation of water in the enzyme mechanism were investigated by X-ray crystallography. The apoenzyme and its complex with adenosine 5'-diphosphoribose have an open protein conformation with the catalytic zinc in one position, tetracoordinated by Cys-46, His-67, Cys-174, and a water molecule. The bidentate chelators 2,2'-bipyridine and 1,10-phenanthroline displace the water and form a pentacoordinated zinc. The enzyme-NADH complex has a closed conformation similar to that of ternary complexes with coenzyme and substrate analogues; the coordination of the catalytic zinc is similar to that found in the apoenzyme, except that a minor, alternative position for the catalytic zinc is ∼1.3 Šfrom the major position and closer to Glu-68, which could form the alternative coordination to the catalytic zinc. Complexes with NADH and N-1-methylhexylformamide or N-benzylformamide (or with NAD and fluoro alcohols) have the classical tetracoordinated zinc, and no water is bound to the zinc or the nicotinamide rings. The major forms of the enzyme in the mechanism have a tetracoordinated zinc, where the carboxylate group of Glu-68 could participate in the exchange of water and substrates on the zinc. Hydride transfer in the Michaelis complexes does not involve a nearby water.
[Mh] Termos MeSH primário: Álcool Desidrogenase/metabolismo
Fígado/enzimologia
Zinco/metabolismo
[Mh] Termos MeSH secundário: 2,2'-Dipiridil/metabolismo
Adenosina Difosfato Ribose/metabolismo
Álcool Desidrogenase/química
Animais
Domínio Catalítico
Cristalografia por Raios X
Formamidas/metabolismo
Cavalos
Cinética
Fígado/metabolismo
Modelos Moleculares
NAD/metabolismo
Fenantrolinas/metabolismo
Ligação Proteica
Conformação Proteica
Água/química
Água/metabolismo
Zinco/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Formamides); 0 (N-benzylformamide); 0 (Phenanthrolines); 059QF0KO0R (Water); 0U46U6E8UK (NAD); 20762-30-5 (Adenosine Diphosphate Ribose); 551W113ZEP (2,2'-Dipyridyl); EC 1.1.1.1 (Alcohol Dehydrogenase); J41CSQ7QDS (Zinc); W4X6ZO7939 (1,10-phenanthroline)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170804
[Lr] Data última revisão:
170804
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170623
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.7b00446


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[PMID]:28581522
[Au] Autor:Song Y; Li S; Ray A; Das DS; Qi J; Samur MK; Tai YT; Munshi N; Carrasco RD; Chauhan D; Anderson KC
[Ad] Endereço:LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
[Ti] Título:Blockade of deubiquitylating enzyme Rpn11 triggers apoptosis in multiple myeloma cells and overcomes bortezomib resistance.
[So] Source:Oncogene;36(40):5631-5638, 2017 Oct 05.
[Is] ISSN:1476-5594
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Proteasome inhibition is an effective therapy for multiple myeloma (MM) patients; however, the emergence of drug resistance is common. Novel therapeutic strategies to overcome proteasome inhibitor resistance are needed. In this study, we examined whether targeting deubiquitylating (DUB) enzymes upstream of 20S proteasome overcomes proteasome inhibitor resistance. Gene expression analysis, immunohistochemical studies of MM patient bone marrow, reverse transcription-PCR and protein analysis show that Rpn11/POH1, a DUB enzyme upstream of 20S proteasome, is more highly expressed in patient MM cells than in normal plasma cells. Importantly, Rpn11 expression directly correlates with poor patient survival. Loss-of-function studies show that Rpn11-siRNA knockdown decreases MM cell viability. Pharmacological inhibition of Rpn11 with O-phenanthroline (OPA) blocks cellular proteasome function, induces apoptosis in MM cells and overcomes resistance to proteasome inhibitor bortezomib. Mechanistically, Rpn11 inhibition in MM cells activates caspase cascade and endoplasmic stress response signaling. Human MM xenograft model studies demonstrate that OPA treatment reduces progression of tumor growth and prolongs survival in mice. Finally, blockade of Rpn11 increases the cytotoxic activity of anti-MM agents lenalidomide, pomalidomide or dexamethasone. Overall, our preclinical data provide the rationale for targeting DUB enzyme Rpn11 upstream of 20S proteasome to enhance cytotoxicity and overcome proteasome inhibitor resistance in MM.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Bortezomib/uso terapêutico
Mieloma Múltiplo/tratamento farmacológico
Inibidores de Proteassoma/uso terapêutico
Transativadores/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Linhagem Celular Tumoral
Proliferação Celular
Resistência a Medicamentos Antineoplásicos
Seres Humanos
Camundongos
Mieloma Múltiplo/enzimologia
Fenantrolinas/farmacologia
Prognóstico
Complexo de Endopeptidases do Proteassoma
Ubiquitinação
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (PSMD14 protein, human); 0 (Phenanthrolines); 0 (Proteasome Inhibitors); 0 (Trans-Activators); 14708-99-7 (ferroin); 69G8BD63PP (Bortezomib); EC 3.4.25.1 (Proteasome Endopeptidase Complex)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171117
[Lr] Data última revisão:
171117
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170606
[St] Status:MEDLINE
[do] DOI:10.1038/onc.2017.172


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[PMID]:28559440
[Au] Autor:Zheng K; Lu P; Delpapa E; Bellve K; Deng R; Condon JC; Fogarty K; Lifshitz LM; Simas TAM; Shi F; ZhuGe R
[Ad] Endereço:College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
[Ti] Título:Bitter taste receptors as targets for tocolytics in preterm labor therapy.
[So] Source:FASEB J;31(9):4037-4052, 2017 Sep.
[Is] ISSN:1530-6860
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Preterm birth (PTB) is the leading cause of neonatal mortality and morbidity, with few prevention and treatment options. Uterine contraction is a central feature of PTB, so gaining new insights into the mechanisms of this contraction and consequently identifying novel targets for tocolytics are essential for more successful management of PTB. Here we report that myometrial cells from human and mouse express bitter taste receptors (TAS2Rs) and their canonical signaling components ( G-protein gustducin and phospholipase C ß2). Bitter tastants can completely relax myometrium precontracted by different uterotonics. In isolated single mouse myometrial cells, a phenotypical bitter tastant (chloroquine, ChQ) reverses the rise in intracellular Ca concentration ([Ca ] ) and cell shortening induced by uterotonics, and this reversal effect is inhibited by pertussis toxin and by genetic deletion of α-gustducin. In human myometrial cells, knockdown of TAS2R14 but not TAS2R10 inhibits ChQ's reversal effect on an oxytocin-induced rise in [Ca ] Finally, ChQ prevents mouse PTBs induced by bacterial endotoxin LPS or progesterone receptor antagonist mifepristone more often than current commonly used tocolytics, and this prevention is largely lost in α-gustducin-knockout mice. Collectively, our results reveal that activation of the canonical TAS2R signaling system in myometrial cells produces profound relaxation of myometrium precontracted by a broad spectrum of contractile agonists, and that targeting TAS2Rs is an attractive approach to developing effective tocolytics for PTB management.-Zheng, K., Lu, P., Delpapa, E., Bellve, K., Deng, R., Condon, J. C., Fogarty, K., Lifshitz, L. M., Simas, T. A. M., Shi, F., ZhuGe, R. Bitter taste receptors as targets for tocolytics in preterm labor therapy.
[Mh] Termos MeSH primário: Regulação da Expressão Gênica/fisiologia
Miométrio/citologia
Trabalho de Parto Prematuro/tratamento farmacológico
Receptores Acoplados a Proteínas-G/metabolismo
[Mh] Termos MeSH secundário: Albuterol
Animais
Cálcio/metabolismo
Cloroquina
Feminino
Seres Humanos
Sulfato de Magnésio
Camundongos
Contração Muscular/efeitos dos fármacos
Contração Muscular/fisiologia
Músculo Liso/efeitos dos fármacos
Músculo Liso/fisiologia
Ocitocina/farmacologia
Fenantrolinas
Gravidez
Compostos de Amônio Quaternário
Receptores Acoplados a Proteínas-G/genética
Transducina/genética
Transducina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Phenanthrolines); 0 (Quaternary Ammonium Compounds); 0 (Receptors, G-Protein-Coupled); 147979-21-3 (gustducin); 4YK5Z54AT2 (denatonium benzoate); 50-56-6 (Oxytocin); 7487-88-9 (Magnesium Sulfate); 886U3H6UFF (Chloroquine); EC 3.6.5.1 (Transducin); QF8SVZ843E (Albuterol); SY7Q814VUP (Calcium); W4X6ZO7939 (1,10-phenanthroline)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170601
[St] Status:MEDLINE
[do] DOI:10.1096/fj.201601323RR


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[PMID]:28557066
[Au] Autor:Arumugam G; Sreeramulu B; Paulchamy R; Thangavel S; Sundaram J
[Ad] Endereço:Department of Zoology, University of Madras, Chennai, India.
[Ti] Título:Purification and functional characterization of lectin with phenoloxidase activity from the hemolymph of cockroach, Periplaneta americana.
[So] Source:Arch Insect Biochem Physiol;95(2), 2017 Jun.
[Is] ISSN:1520-6327
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Lectins also identified as hemagglutinins are multivalent proteins and on account of their fine sugar-binding specificity play an important role in immune system of invertebrates. The present study was carried out on the hemolymph lectin of cockroach, Periplaneta americana with appropriate screening and purification to understand its molecular as well as functional nature. The lectin from the hemolymph was purified using ion-exchange chromatography. The approximate molecular weight of purified lectin was 340 kDa as determined by FPLC analysis. Rabbit erythrocytes were highly agglutinated with purified lectin from the hemolymph of P. americana. The hemagglutination activity (HA) of lectin was specifically inhibited by fucose. Glycoproteins also inhibited the HA activity of lectin. The amino acid sequences of the purified lectin revealed homology with amino acid sequences of allergen proteins from P. americana. Purified lectin showed the highest phenoloxidase activity against dopamine. The activators such as exogenous proteases and LPS from Escherichia coli and Salmonella minnesota significantly enhanced the PO activity of the purified lectin. Besides, the presence of copper and hemocyanin conserved domain in the purified lectin provided a new facet that insects belonging to the ancient clade such as cockroaches retained some traces of evolutionary resemblance in possessing lectin of ancient origin.
[Mh] Termos MeSH primário: Lectinas/isolamento & purificação
Monofenol Mono-Oxigenase/metabolismo
Periplaneta/enzimologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Eletroforese em Gel de Poliacrilamida
Hemaglutinação
Hemolinfa/metabolismo
Lectinas/metabolismo
Monofenol Mono-Oxigenase/antagonistas & inibidores
Oxirredução
Fenantrolinas
Feniltioureia
Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Lectins); 0 (Phenanthrolines); 6F82C6Q54C (Phenylthiourea); 73348-75-1 (bathocuproine sulfonate); EC 1.14.18.1 (Monophenol Monooxygenase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170531
[St] Status:MEDLINE
[do] DOI:10.1002/arch.21390


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[PMID]:28475937
[Au] Autor:Warad I; Awwadi FF; Daqqa M; Al Ali A; Ababneh TS; AlShboul TMA; Jazzazi TMA; Al-Rimawi F; Hadda TB; Mabkhot YN
[Ad] Endereço:Department of Chemistry, Science College, An-Najah National University, P.O. Box 7, Nablus, Palestine. Electronic address: warad@najah.edu.
[Ti] Título:New isomeric Cu(NO -phen) Br]Br complexes: Crystal structure, Hirschfeld surface, physicochemical, solvatochromism, thermal, computational and DNA-binding analysis.
[So] Source:J Photochem Photobiol B;171:9-19, 2017 Jun.
[Is] ISSN:1873-2682
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Water soluble mono-cationic copper(II) complex of the general formula [Cu(NO -phen) Br]Br, (NO -phen=5-nitro-1.10-phenantholine) was prepared in good yield under ultrasonic irradiation. The desired complex was isolated as a bromide salt and identified by MS, EA, UV-Vis., TG/DTA, FT-IR and XRD. The single-crystal X-ray diffraction and Hirschfield analysis revealed a square pyramidal distorted geometry around the Cu(II) center. The geometry of the [Cu(NO -phen) Br] complex was fully optimized with ab-initio methods and (DFT/B3LYP) density functional theory, then structural parameters were compared to the XRD data. The solvatochromism of [Cu(NO -phen) Br]Br complex was investigated in several polar solvents. Absorption and viscosity titration studies concluded that the [Cu(NO -phen) Br]Br complex is a very good CT-DNA binder.
[Mh] Termos MeSH primário: Complexos de Coordenação/química
Cobre/química
Solventes/química
[Mh] Termos MeSH secundário: Animais
Bovinos
Cobre/metabolismo
Cristalografia por Raios X
DNA/química
DNA/metabolismo
Isomerismo
Conformação Molecular
Óxidos de Nitrogênio/química
Fenantrolinas/química
Espectrofotometria Ultravioleta
Espectroscopia de Infravermelho com Transformada de Fourier
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Coordination Complexes); 0 (Nitrogen Oxides); 0 (Phenanthrolines); 0 (Solvents); 789U1901C5 (Copper); 9007-49-2 (DNA); 91080-16-9 (calf thymus DNA)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170920
[Lr] Data última revisão:
170920
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170506
[St] Status:MEDLINE



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