Base de dados : MEDLINE
Pesquisa : D08.811.520.241.300.150.200 [Categoria DeCS]
Referências encontradas : 983 [refinar]
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[PMID]:29289880
[Au] Autor:Ansari MF; Idrees D; Hassan MI; Ahmad K; Avecilla F; Azam A
[Ad] Endereço:Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, 110 025, New Delhi, India.
[Ti] Título:Design, synthesis and biological evaluation of novel pyridine-thiazolidinone derivatives as anticancer agents: Targeting human carbonic anhydrase IX.
[So] Source:Eur J Med Chem;144:544-556, 2018 Jan 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:In order to obtain novel Human carbonic anhydrase IX (CAIX) inhibitors, a series of pyridine-thiazolidinone derivatives was synthesized and characterized by various spectroscopic techniques. The binding affinity of the compounds was measured by fluorescence binding studies and enzyme inhibition activity using esterase assay of CAIX. It was observed that compound 8 and 11 significantly inhibit the CAIX activity with the IC value, 1.61 µM and 1.84 µM, respectively. The binding-affinity of compound 8 and 11 for CAIX was significantly high with their K values 11.21 µM and 2.32 µM, respectively. Docking studies revealed that compound 8 and 11 efficiently binds in the active site cavity of CA IX by forming sufficient numbers of H-bonds and van der Waals interactions with active side residues. All the compounds were further screened in vitro for anticancer activity and found that compound 8 and 11 exhibit considerable anticancer activity against MCF-7 and HepG-2 cell lines. All these findings suggest that compound 8 and 11 may be further exploited as a novel pharmacophore model for the development of anticancer agents.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Anidrase Carbônica IX/antagonistas & inibidores
Inibidores da Anidrase Carbônica/farmacologia
Desenho de Drogas
Piridinas/farmacologia
Tiazolidinas/farmacologia
[Mh] Termos MeSH secundário: Antígenos de Neoplasias/metabolismo
Antineoplásicos/síntese química
Antineoplásicos/química
Anidrase Carbônica II/antagonistas & inibidores
Anidrase Carbônica II/metabolismo
Anidrase Carbônica IX/metabolismo
Inibidores da Anidrase Carbônica/síntese química
Inibidores da Anidrase Carbônica/química
Proliferação Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Simulação de Acoplamento Molecular
Estrutura Molecular
Piridinas/síntese química
Piridinas/química
Relação Estrutura-Atividade
Tiazolidinas/síntese química
Tiazolidinas/química
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Neoplasm); 0 (Antineoplastic Agents); 0 (Carbonic Anhydrase Inhibitors); 0 (Pyridines); 0 (Thiazolidines); EC 4.2.1.- (Carbonic Anhydrase II); EC 4.2.1.1 (CA9 protein, human); EC 4.2.1.1 (Carbonic Anhydrase IX); NH9L3PP67S (pyridine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180101
[St] Status:MEDLINE


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[PMID]:29280407
[Au] Autor:Angeli A; Chiaramonte N; Manetti D; Romanelli MN; Supuran CT
[Ad] Endereço:a Dipartimento Neurofarba , Università degli Studi di Firenze, Sezione di Scienze Farmaceutiche e Nutraceutiche , Sesto Fiorentino (Florence) , Italy.
[Ti] Título:Investigation of piperazines as human carbonic anhydrase I, II, IV and VII activators.
[So] Source:J Enzyme Inhib Med Chem;33(1):303-308, 2018 Dec.
[Is] ISSN:1475-6374
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Four human (h) carbonic anhydrase isoforms (CA, EC 4.2.1.1), hCA I, II, IV, and VII, were investigated for their activation profile with piperazines belonging to various classes, such as N-aryl-, N-alkyl-, N-acyl-piperazines as well as 2,4-disubstituted derivatives. As the activation mechanism involves participation of the activator in the proton shuttling between the zinc-coordinated water molecule and the external milieu, these derivatives possessing diverse basicity and different scaffolds were appropriate for being investigated as CA activators (CAAs). Most of these derivatives showed CA activating properties against hCA I, II, and VII (cytosolic isoforms) but were devoid of activity against the membrane-associated hCA IV. For hCA I, the K s were in the range of 32.6-131 µM; for hCA II of 16.2-116 µM, and for hCA VII of 17.1-131 µM. The structure-activity relationship was intricate and not easy to rationalize, but the most effective activators were 1-(2-piperidinyl)-piperazine (K of 16.2 µM for hCA II), 2-benzyl-piperazine (K of 17.1 µM for hCA VII), and 1-(3-benzylpiperazin-1-yl)propan-1-one (K of 32.6 µM for hCA I). As CAAs may have interesting pharmacologic applications in cognition and for artificial tissue engineering, investigation of new classes of activators may be crucial for this relatively new research field.
[Mh] Termos MeSH primário: Anidrase Carbônica II/antagonistas & inibidores
Anidrase Carbônica IV/antagonistas & inibidores
Anidrase Carbônica I/antagonistas & inibidores
Inibidores da Anidrase Carbônica/farmacologia
Anidrases Carbônicas/metabolismo
Piperazinas/farmacologia
[Mh] Termos MeSH secundário: Anidrase Carbônica I/metabolismo
Anidrase Carbônica II/metabolismo
Anidrase Carbônica IV/metabolismo
Inibidores da Anidrase Carbônica/síntese química
Inibidores da Anidrase Carbônica/química
Relação Dose-Resposta a Droga
Seres Humanos
Modelos Moleculares
Estrutura Molecular
Piperazinas/síntese química
Piperazinas/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carbonic Anhydrase Inhibitors); 0 (Piperazines); EC 4.2.1.- (Carbonic Anhydrase I); EC 4.2.1.- (Carbonic Anhydrase II); EC 4.2.1.- (Carbonic Anhydrase IV); EC 4.2.1.1 (CA4 protein, human); EC 4.2.1.1 (Carbonic Anhydrases); EC 4.2.1.1 (carbonic anhydrase VI)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180105
[Lr] Data última revisão:
180105
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171228
[St] Status:MEDLINE
[do] DOI:10.1080/14756366.2017.1417277


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[PMID]:29199489
[Au] Autor:Alterio V; Esposito D; Monti SM; Supuran CT; De Simone G
[Ad] Endereço:a Istituto di Biostrutture e Bioimagini-CNR , Naples , Italy.
[Ti] Título:Crystal structure of the human carbonic anhydrase II adduct with 1-(4-sulfamoylphenyl-ethyl)-2,4,6-triphenylpyridinium perchlorate, a membrane-impermeant, isoform selective inhibitor.
[So] Source:J Enzyme Inhib Med Chem;33(1):151-157, 2018 Dec.
[Is] ISSN:1475-6374
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Pyridinium containing sulfonamides have been largely investigated as carbonic anhydrase inhibitors (CAIs), showing interesting selectivity features. Nevertheless, only few structural studies are so far available on adducts that these compounds form with diverse CA isoforms. In this paper, we report the structural characterization of the adduct that a triphenylpyridinium derivative forms with hCA II, showing that the substitution of the pyridinium ring plays a key role in determining the conformation of the inhibitor in the active site and consequently the binding affinity to the enzyme. These findings open new perspectives on the basic structural requirements for designing sulfonamide CAIs with a selective inhibition profile.
[Mh] Termos MeSH primário: Anidrase Carbônica II/antagonistas & inibidores
Inibidores da Anidrase Carbônica/farmacologia
Compostos de Piridínio/farmacologia
Sulfonamidas/farmacologia
[Mh] Termos MeSH secundário: Anidrase Carbônica II/metabolismo
Inibidores da Anidrase Carbônica/química
Cristalografia por Raios X
Relação Dose-Resposta a Droga
Seres Humanos
Modelos Moleculares
Estrutura Molecular
Compostos de Piridínio/síntese química
Compostos de Piridínio/química
Relação Estrutura-Atividade
Sulfonamidas/síntese química
Sulfonamidas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (1-(4-sulfamoylphenylethyl)-2,4,6-triphenylpyridinium); 0 (Carbonic Anhydrase Inhibitors); 0 (Pyridinium Compounds); 0 (Sulfonamides); EC 4.2.1.- (Carbonic Anhydrase II)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171219
[Lr] Data última revisão:
171219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171205
[St] Status:MEDLINE
[do] DOI:10.1080/14756366.2017.1405263


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[PMID]:28464340
[Au] Autor:Aktas A; Taslimi P; Gülçin I; Gök Y
[Ad] Endereço:Faculty of Arts and Sciences, Department of Chemistry, Inönü University, Malatya, Turkey.
[Ti] Título:Novel NHC Precursors: Synthesis, Characterization, and Carbonic Anhydrase and Acetylcholinesterase Inhibitory Properties.
[So] Source:Arch Pharm (Weinheim);350(6), 2017 Jun.
[Is] ISSN:1521-4184
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Three series of imidazolidinium ligands (NHC precursors) substituted with 4-vinylbenzyl, 2-methyl-1,4-benzodioxane, and N-propylphthalimide were synthesized. N-Heterocyclic carbene (NHC) precursors were prepared from N-alkylimidazoline and alkyl halides. The novel NHC precursors were characterized by H NMR, C NMR, FTIR spectroscopy, and elemental analysis techniques. The enzymes inhibition activities of the NHC precursors were investigated against the cytosolic human carbonic anhydrase I and II isoenzymes (hCA I and II) and the acetylcholinesterase (AChE) enzyme. The inhibition parameters (IC and K values) were calculated by spectrophotometric method. The inhibition constants (K ) were found to be in the range of 166.65-635.38 nM for hCA I, 78.79-246.17 nM for hCA II, and 23.42-62.04 nM for AChE. Also, the inhibitory effects of the novel synthesized NHCs were compared to acetazolamide as a clinical CA isoenzymes inhibitor and tacrine as a clinical cholinergic enzymes inhibitor.
[Mh] Termos MeSH primário: Inibidores da Anidrase Carbônica/farmacologia
Inibidores da Colinesterase/farmacologia
Compostos Heterocíclicos/farmacologia
Imidazolidinas/farmacologia
Metano/análogos & derivados
[Mh] Termos MeSH secundário: Acetilcolinesterase/metabolismo
Anidrase Carbônica I/antagonistas & inibidores
Anidrase Carbônica I/metabolismo
Anidrase Carbônica II/antagonistas & inibidores
Anidrase Carbônica II/metabolismo
Inibidores da Anidrase Carbônica/síntese química
Inibidores da Anidrase Carbônica/química
Inibidores da Colinesterase/síntese química
Inibidores da Colinesterase/química
Relação Dose-Resposta a Droga
Compostos Heterocíclicos/síntese química
Compostos Heterocíclicos/química
Seres Humanos
Imidazolidinas/síntese química
Imidazolidinas/química
Ligantes
Metano/síntese química
Metano/química
Metano/farmacologia
Estrutura Molecular
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carbonic Anhydrase Inhibitors); 0 (Cholinesterase Inhibitors); 0 (Heterocyclic Compounds); 0 (Imidazolidines); 0 (Ligands); 2465-56-7 (carbene); EC 3.1.1.7 (Acetylcholinesterase); EC 4.2.1.- (Carbonic Anhydrase I); EC 4.2.1.- (Carbonic Anhydrase II); OP0UW79H66 (Methane)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171201
[Lr] Data última revisão:
171201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1002/ardp.201700045


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[PMID]:28965419
[Au] Autor:Ramya PVS; Angapelly S; Angeli A; Digwal CS; Arifuddin M; Babu BN; Supuran CT; Kamal A
[Ad] Endereço:a Department of Medicinal Chemistry , National Institute of Pharmaceutical Education and Research (NIPER) , Hyderabad , India.
[Ti] Título:Discovery of curcumin inspired sulfonamide derivatives as a new class of carbonic anhydrase isoforms I, II, IX, and XII inhibitors.
[So] Source:J Enzyme Inhib Med Chem;32(1):1274-1281, 2017 Dec.
[Is] ISSN:1475-6374
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A series of curcumin inspired sulfonamide derivatives was prepared from various chalcones and 4-sulfamoyl benzaldehyde via Claisen-Schmidt condensation. All new compounds were assayed as inhibitors of four human isoforms of the metalloenzyme carbonic anhydrase (hCA, EC 4.2.1.1) isoforms hCA I, II, IX and XII. Interesting inhibitory activities were observed against all these isoforms. hCA I, an isoform involved in several eye diseases was inhibited moderately with K s in the range of 191.8-904.2 nM, hCA II, an antiglaucoma drug target was highly inhibited by the new sulfonamides, with K s in the range of 0.75-8.8 nM. hCA IX, a tumor-associated isoform involved in cancer progression and metastatic spread was potently inhibited by the new sulfonamides, with K s in the range of 2.3-87.3 nM, whereas hCA XII, and antiglaucoma and anticancer drug target, was inhibited with K s in the range of 6.1-71.8 nM. It is noteworthy that one of the new compounds, 5d, was found to be almost 9 times more selective against hCA II (K = 0.89 nM) over hCA IX and hCA XII, whereas 5e was 3 and 70 times more selective against hCA II (K = 0.75 nM) over hCA IX and hCA XII, respectively.
[Mh] Termos MeSH primário: Inibidores da Anidrase Carbônica/farmacologia
Curcumina/farmacologia
Descoberta de Drogas
Sulfonamidas/farmacologia
[Mh] Termos MeSH secundário: Antígenos de Neoplasias/metabolismo
Anidrase Carbônica I/antagonistas & inibidores
Anidrase Carbônica I/metabolismo
Anidrase Carbônica II/antagonistas & inibidores
Anidrase Carbônica II/metabolismo
Anidrase Carbônica IX/antagonistas & inibidores
Anidrase Carbônica IX/metabolismo
Inibidores da Anidrase Carbônica/síntese química
Inibidores da Anidrase Carbônica/química
Anidrases Carbônicas/metabolismo
Curcumina/síntese química
Curcumina/química
Relação Dose-Resposta a Droga
Seres Humanos
Estrutura Molecular
Relação Estrutura-Atividade
Sulfonamidas/síntese química
Sulfonamidas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Neoplasm); 0 (Carbonic Anhydrase Inhibitors); 0 (Sulfonamides); EC 4.2.1.- (Carbonic Anhydrase I); EC 4.2.1.- (Carbonic Anhydrase II); EC 4.2.1.1 (CA9 protein, human); EC 4.2.1.1 (Carbonic Anhydrase IX); EC 4.2.1.1 (Carbonic Anhydrases); EC 4.2.1.1 (carbonic anhydrase XII); IT942ZTH98 (Curcumin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171003
[St] Status:MEDLINE
[do] DOI:10.1080/14756366.2017.1380638


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[PMID]:28940980
[Au] Autor:Angapelly S; Sri Ramya PV; Angeli A; Supuran CT; Arifuddin M
[Ad] Endereço:Department of Medicinal Chemistry, National Institute of Pharmaceutical Education & Research (NIPER), Hyderabad, 500037, India.
[Ti] Título:Sulfocoumarin-, Coumarin-, 4-Sulfamoylphenyl-Bearing Indazole-3-carboxamide Hybrids: Synthesis and Selective Inhibition of Tumor-Associated Carbonic Anhydrase Isozymes IX and XII.
[So] Source:ChemMedChem;12(19):1578-1584, 2017 Oct 09.
[Is] ISSN:1860-7187
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:A series of sulfocoumarin-, coumarin-, and 4-sulfamoylphenyl-bearing indazole-3-carboxamide hybrids were synthesized and investigated as inhibitors of the human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms I and II (cytosolic isozymes), as well as hCA IX and XII (transmembrane, tumor-associated enzymes). Compounds 6 a-g (amide derivatives) and 7 a-h (triazoles) act as "prodrugs", and their hydrolysis products are the de facto CA inhibitors. These compounds displayed sub-micromolar to high-nanomolar inhibitory activity against hCA isoforms IX and XII, which were recently validated as antitumor drug targets. Moreover, no inhibition of the off-target hCA I and II isoforms was observed. Compounds 8 a-f (another set of triazoles) exhibited nanomolar inhibition against hCA isoforms I, II, IX and XII, among which compounds 8 c, 8 d, and 8 f were found to inhibit the tumor-associated hypoxia-induced hCA isoform IX with K values of 1.8, 2.3, and 2.0 nm respectively. Further exploration of these compounds could be useful for the development of novel antitumor agents with selective mechanisms of CA inhibitory action.
[Mh] Termos MeSH primário: Amidas/química
Anidrase Carbônica IX/metabolismo
Inibidores da Anidrase Carbônica/síntese química
Anidrases Carbônicas/metabolismo
Cumarínicos/química
[Mh] Termos MeSH secundário: Amidas/síntese química
Amidas/metabolismo
Sítios de Ligação
Anidrase Carbônica I/antagonistas & inibidores
Anidrase Carbônica I/metabolismo
Anidrase Carbônica II/antagonistas & inibidores
Anidrase Carbônica II/metabolismo
Anidrase Carbônica IX/antagonistas & inibidores
Inibidores da Anidrase Carbônica/química
Inibidores da Anidrase Carbônica/metabolismo
Anidrases Carbônicas/química
Domínio Catalítico
Cumarínicos/síntese química
Cumarínicos/metabolismo
Seres Humanos
Indazóis/química
Concentração Inibidora 50
Isoenzimas/antagonistas & inibidores
Isoenzimas/metabolismo
Simulação de Dinâmica Molecular
Neoplasias/enzimologia
Neoplasias/patologia
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amides); 0 (Carbonic Anhydrase Inhibitors); 0 (Coumarins); 0 (Indazoles); 0 (Isoenzymes); EC 4.2.1.- (Carbonic Anhydrase I); EC 4.2.1.- (Carbonic Anhydrase II); EC 4.2.1.1 (Carbonic Anhydrase IX); EC 4.2.1.1 (Carbonic Anhydrases); EC 4.2.1.1 (carbonic anhydrase XII)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170924
[St] Status:MEDLINE
[do] DOI:10.1002/cmdc.201700446


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[PMID]:28891338
[Au] Autor:Kumar R; Sharma V; Bua S; Supuran CT; Sharma PK
[Ad] Endereço:a Department of Chemistry , Kurukshetra University , Kurukshetra , India.
[Ti] Título:Synthesis and biological evaluation of benzenesulphonamide-bearing 1,4,5-trisubstituted-1,2,3-triazoles possessing human carbonic anhydrase I, II, IV, and IX inhibitory activity.
[So] Source:J Enzyme Inhib Med Chem;32(1):1187-1194, 2017 Dec.
[Is] ISSN:1475-6374
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A library of benzenesulphonamides incorporating 1,2,3-triazole rings functionalised with ester, carboxylic acid, carboxamide, carboxyhydrazide, and hydroxymethyl moieties were synthesised. The carbonic anhydrase (CAs, EC 4.2.1.1) inhibitory activity of the new compounds was assessed against four human (h) isoforms, hCA I, hCA II, hCA IV, and hCA IX. Among them, hCA II and IV are anti-glaucoma drug targets, being involved in aqueous humour secretion within the eye. hCA I was inhibited with Ki's ranging between 8.3 nM and 0.8737 µM. hCA II, the physiologically dominant cytosolic isoform, was excellently inhibited by these compounds, with Ki's in the range of 1.6-9.4 nM, whereas hCA IV was effectively inhibited by most of them, with Ki's in the range of 1.4-55.3 nM. Thirteen of the twenty sulphonamides were found to be excellent inhibitors of tumour associated hCA IX with Ki's ≤ 9.5 nM. Many of the new compounds reported here showed low nM inhibitory action against hCA II, IV, and IX, isoforms involved in glaucoma and some tumours, making them interesting candidates for further medicinal chemistry/pharmacologic studies.
[Mh] Termos MeSH primário: Inibidores da Anidrase Carbônica/farmacologia
Sulfonamidas/farmacologia
Triazóis/farmacologia
[Mh] Termos MeSH secundário: Anidrase Carbônica I/antagonistas & inibidores
Anidrase Carbônica I/metabolismo
Anidrase Carbônica II/antagonistas & inibidores
Anidrase Carbônica II/metabolismo
Anidrase Carbônica IV/antagonistas & inibidores
Anidrase Carbônica IV/metabolismo
Anidrase Carbônica IX/antagonistas & inibidores
Anidrase Carbônica IX/metabolismo
Inibidores da Anidrase Carbônica/síntese química
Inibidores da Anidrase Carbônica/química
Relação Dose-Resposta a Droga
Seres Humanos
Estrutura Molecular
Relação Estrutura-Atividade
Sulfonamidas/síntese química
Sulfonamidas/química
Triazóis/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carbonic Anhydrase Inhibitors); 0 (Sulfonamides); 0 (Triazoles); 98-10-2 (benzenesulfonamide); EC 4.2.1.- (Carbonic Anhydrase I); EC 4.2.1.- (Carbonic Anhydrase II); EC 4.2.1.- (Carbonic Anhydrase IV); EC 4.2.1.1 (Carbonic Anhydrase IX)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170912
[St] Status:MEDLINE
[do] DOI:10.1080/14756366.2017.1367775


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[PMID]:28866249
[Au] Autor:Akincioglu A; Kocaman E; Akincioglu H; Salmas RE; Durdagi S; Gülçin I; Supuran CT; Göksu S
[Ad] Endereço:Atatürk University, Faculty of Science, Department of Chemistry, Erzurum, Turkey; Agri Ibrahim Çeçen University, Central Researching Laboratory, Agri, Turkey.
[Ti] Título:The synthesis of novel sulfamides derived from ß-benzylphenethylamines as acetylcholinesterase, butyrylcholinesterase and carbonic anhydrase enzymes inhibitors.
[So] Source:Bioorg Chem;74:238-250, 2017 Oct.
[Is] ISSN:1090-2120
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In this study, a series of novel ß-benzylphenethylamines and their sulfamide derivatives were synthesized starting from (Z)-2,3-diphenylacrylonitriles. Pd-C catalysed hydrogenation of diphenylacrylonitriles, reduction of propanenitriles with LiAlH in the presence of AlCl followed by addition of conc. HCl afforded ß-benzylphenethylamine hydrochloride salts. The reactions of these amine hydrochloride salts with chlorosulfonyl isocyanate (CSI) in the presence of tert-BuOH and excess Et N gave sulfamoylcarbamates. Removing of Boc group from the synthesized sulfamoylcarbamates with trifluoroacetic acid (TFA) yielded novel sulfamides in good yields. These novel sulfamides derived from ß-benzylphenethylamines were effective inhibitors of the cytosolic carbonic anhydrase I and II isoenzymes (hCA I and II), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with K values in the range of 0.278-2.260nM for hCA I, 0.187-1.478nM for hCA II, 0.127-2.452nM for AChE and 0.494-1.790nM for BChE. The inhibitory effects of the synthesized novel sulfamides derived from ß-benzylphenethylamines were compared to those of acetazolamide and dorzolamide as clinical hCA I and II isoenzymes inhibitors and tacrine as a clinical AChE and BChE enzymes inhibitors. In addition to in vitro tests, molecular modeling approaches are implemented not only for prediction of the binding affinities of the compounds but also to study their inhibition mechanisms in atomic level at the catalytic domains.
[Mh] Termos MeSH primário: Compostos de Benzil/farmacologia
Inibidores da Anidrase Carbônica/farmacologia
Inibidores da Colinesterase/farmacologia
Etilaminas/farmacologia
Sulfonamidas/farmacologia
[Mh] Termos MeSH secundário: Acetilcolinesterase/metabolismo
Compostos de Benzil/química
Butirilcolinesterase/metabolismo
Anidrase Carbônica I/metabolismo
Anidrase Carbônica II/metabolismo
Inibidores da Anidrase Carbônica/síntese química
Inibidores da Anidrase Carbônica/química
Inibidores da Colinesterase/síntese química
Inibidores da Colinesterase/química
Relação Dose-Resposta a Droga
Etilaminas/química
Seres Humanos
Modelos Moleculares
Estrutura Molecular
Relação Estrutura-Atividade
Sulfonamidas/síntese química
Sulfonamidas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzyl Compounds); 0 (Carbonic Anhydrase Inhibitors); 0 (Cholinesterase Inhibitors); 0 (Ethylamines); 0 (Sulfonamides); 0 (beta-benzylphenethylamine); EC 3.1.1.7 (Acetylcholinesterase); EC 3.1.1.8 (Butyrylcholinesterase); EC 4.2.1.- (Carbonic Anhydrase I); EC 4.2.1.- (Carbonic Anhydrase II)
[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:170904
[St] Status:MEDLINE


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[PMID]:28817930
[Au] Autor:Chrysanthopoulos PK; Mujumdar P; Woods LA; Dolezal O; Ren B; Peat TS; Poulsen SA
[Ad] Endereço:Griffith University , Griffith Institute for Drug Discovery, Nathan, Brisbane, Queensland 4111, Australia.
[Ti] Título:Identification of a New Zinc Binding Chemotype by Fragment Screening.
[So] Source:J Med Chem;60(17):7333-7349, 2017 Sep 14.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The discovery of a new zinc binding chemotype from screening a nonbiased fragment library is reported. Using the orthogonal fragment screening methods of native state mass spectrometry and surface plasmon resonance a 3-unsubstituted 2,4-oxazolidinedione fragment was found to have low micromolar binding affinity to the zinc metalloenzyme carbonic anhydrase II (CA II). This affinity approached that of fragment sized primary benzenesulfonamides, the classical zinc binding group found in most CA II inhibitors. Protein X-ray crystallography established that 3-unsubstituted 2,4-oxazolidinediones bound to CA II via an interaction of the acidic ring nitrogen with the CA II active site zinc, as well as two hydrogen bonds between the oxazolidinedione ring oxygen and the CA II protein backbone. Furthermore, 3-unsubstituted 2,4-oxazolidinediones appear to be a viable starting point for the development of an alternative class of CA inhibitor, wherein the medicinal chemistry pedigree of primary sulfonamides has dominated for several decades.
[Mh] Termos MeSH primário: Anidrase Carbônica II/antagonistas & inibidores
Inibidores da Anidrase Carbônica/química
Inibidores da Anidrase Carbônica/farmacologia
Oxazolidinonas/química
Oxazolidinonas/farmacologia
Zinco/metabolismo
[Mh] Termos MeSH secundário: Anidrase Carbônica II/metabolismo
Cristalografia por Raios X
Seres Humanos
Simulação de Acoplamento Molecular
Relação Estrutura-Atividade
Sulfonamidas/química
Sulfonamidas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carbonic Anhydrase Inhibitors); 0 (Oxazolidinones); 0 (Sulfonamides); 98-10-2 (benzenesulfonamide); EC 4.2.1.- (Carbonic Anhydrase II); J41CSQ7QDS (Zinc)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170819
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.7b00606


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[PMID]:28753093
[Au] Autor:Abdoli M; Angeli A; Bozdag M; Carta F; Kakanejadifard A; Saeidian H; Supuran CT
[Ad] Endereço:a Department of Chemistry, Faculty of Science , Lorestan University , Khorramabad , Iran.
[Ti] Título:Synthesis and carbonic anhydrase I, II, VII, and IX inhibition studies with a series of benzo[d]thiazole-5- and 6-sulfonamides.
[So] Source:J Enzyme Inhib Med Chem;32(1):1071-1078, 2017 Dec.
[Is] ISSN:1475-6374
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A series of benzo[d]thiazole-5- and 6-sulfonamides has been synthesized and investigated for the inhibition of several human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms, using ethoxzolamide (EZA) as lead molecule. 2-Amino-substituted, 2-acylamino- and halogenated (bromo-and iodo-derivatives at the heterocyclic ring) compounds led to several interesting inhibitors against the cytosolic hCA I, II and VII, as well as the transmembrane, tumor-associated hCA IX isoforms. Several subnanomolar/low nanomolar, isoform-selective sulfonamide inhibitors targeting hCA II, VII and IX were detected. The sharp structure-activity relationship for CA inhibition with this small series of derivatives, with important changes of activity observed even after minor changes in the scaffold or at the 2-amino moiety, make this class of scarcely investigated sulfonamides of particular interest for further investigations.
[Mh] Termos MeSH primário: Benzotiazóis/farmacologia
Anidrase Carbônica II/antagonistas & inibidores
Anidrase Carbônica IX/antagonistas & inibidores
Anidrase Carbônica I/antagonistas & inibidores
Inibidores da Anidrase Carbônica/farmacologia
Anidrases Carbônicas/metabolismo
Sulfonamidas/farmacologia
[Mh] Termos MeSH secundário: Benzotiazóis/síntese química
Benzotiazóis/química
Anidrase Carbônica I/metabolismo
Anidrase Carbônica II/metabolismo
Anidrase Carbônica IX/metabolismo
Inibidores da Anidrase Carbônica/síntese química
Inibidores da Anidrase Carbônica/química
Relação Dose-Resposta a Droga
Seres Humanos
Estrutura Molecular
Relação Estrutura-Atividade
Sulfonamidas/síntese química
Sulfonamidas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzothiazoles); 0 (Carbonic Anhydrase Inhibitors); 0 (Sulfonamides); EC 4.2.1.- (Carbonic Anhydrase I); EC 4.2.1.- (Carbonic Anhydrase II); EC 4.2.1.1 (Carbonic Anhydrase IX); EC 4.2.1.1 (Carbonic Anhydrases); EC 4.2.1.1 (carbonic anhydrase VI)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170729
[St] Status:MEDLINE
[do] DOI:10.1080/14756366.2017.1356295



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