Base de dados : MEDLINE
Pesquisa : D02.092.650 [Categoria DeCS]
Referências encontradas : 478 [refinar]
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[PMID]:28557987
[Au] Autor:Funk P; Motyka K; Soural M; Malon M; Koshino H; Kusz J; Hlavac J
[Ad] Endereço:Department of Organic Chemistry, Institute of Molecular and Translational Medicine, Faculty of Science, Palacky University, Olomouc, Czech Republic.
[Ti] Título:Study of 2-aminoquinolin-4(1H)-one under Mannich and retro-Mannich reaction.
[So] Source:PLoS One;12(5):e0175364, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:2-Aminoquinolin-4(1H)-one was reacted with various primary/secondary amines and paraformaldehyde under Mannich reaction conditions. In the case of secondary amines, the reaction in N,N-dimethylformamide yielded expected Mannich products accompanied with 3,3'-methylenebis(2-aminoquinolin-4(1H)-one). Except these main products, the pyrimido[4,5-b]quinolin-5-one derivative was also identified as co-product. The reaction with primary amines led to the formation of pyrimido[4,5-b]quinolin-5-ones. The Mannich reaction products were thermally unstable and afforded a mixture of bis-(2-aminoquinolin-4(1H)-one) and tris-(2-aminoquinolin-4(1H)-one) derivative, probably via reactive methylene species. This retro-Mannich reaction was tested in reaction with indole and thiophenole as nucleophilles, and appropriate conjugates were formed. The mechanism of above discussed reactions in which 2-aminoquinolinone displays the nucleophilicity on C3 carbon as well as N2 nitrogen is discussed.
[Mh] Termos MeSH primário: Aminoquinolinas/química
Bases de Mannich/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aminoquinolines); 0 (Mannich Bases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170921
[Lr] Data última revisão:
170921
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170531
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0175364


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[PMID]:28340368
[Au] Autor:Jose G; Suresha Kumara TH; Sowmya HBV; Sriram D; Guru Row TN; Hosamani AA; More SS; Janardhan B; Harish BG; Telkar S; Ravikumar YS
[Ad] Endereço:Department of Chemistry, Jain University, Bangalore 560024, Karnataka, India.
[Ti] Título:Synthesis, molecular docking, antimycobacterial and antimicrobial evaluation of new pyrrolo[3,2-c]pyridine Mannich bases.
[So] Source:Eur J Med Chem;131:275-288, 2017 May 05.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:In this report, we describe the synthesis and biological evaluation of a new series of pyrrolo[3,2-c]pyridine Mannich bases (7a-v). The Mannich bases were obtained in good yields by one-pot three component condensation of pyrrolo[3,2-c]pyridine scaffold (6a-c) with secondary amines and excess of formaldehyde solution in AcOH. The chemical structures of the compounds were characterized by H NMR, C NMR, LC/MS and elemental analysis. Single crystal X-ray diffraction has been recorded for compound 7k ([C H ClN ] , H O). The in vitro antimicrobial activities of the compounds were evaluated against various bacterial and fungal strains using Agar diffusion method and Broth micro dilution method. Compounds 7e, 7f, 7r, 7t, and 7u were showed good Gram-positive antibacterial activity against S. aureus, B. flexus, C. sporogenes and S. mutans. Furthermore, in vitro antimycobacterial activity was evaluated against Mycobacterium tuberculosis H37Rv (ATCC 27294) using MABA. Compounds 7r, 7t, and 7u were showed good antitubercular activity against Mtb (MIC ≥6.25 µg/mL). Among the tested compounds, 1-((4-chloro-2-(cyclohexylmethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)methyl)piperidine-3-carboxamide (7t) was showed excellent antimycobacterial activity against Mtb (MIC <0.78 µg/mL) and low cytotoxicity against the HEK-293T cell line (SI >>25). Molecular docking of the active compounds against glutamate racemase (MurI) and Mtb glutamine synthetase were explained the structure-activity observed in vitro.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Antifúngicos/farmacologia
Bactérias/efeitos dos fármacos
Fungos/efeitos dos fármacos
Simulação de Acoplamento Molecular
Piridinas/farmacologia
Pirróis/farmacologia
[Mh] Termos MeSH secundário: Antibacterianos/síntese química
Antibacterianos/química
Antifúngicos/síntese química
Antifúngicos/química
Sobrevivência Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Células HEK293
Seres Humanos
Bases de Mannich/síntese química
Bases de Mannich/química
Bases de Mannich/farmacologia
Testes de Sensibilidade Microbiana
Estrutura Molecular
Piridinas/síntese química
Piridinas/química
Pirróis/síntese química
Pirróis/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Antifungal Agents); 0 (Mannich Bases); 0 (Pyridines); 0 (Pyrroles); 0 (pyrrolo(3,2-c)pyridine)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170603
[Lr] Data última revisão:
170603
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170325
[St] Status:MEDLINE


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[PMID]:28267984
[Au] Autor:Yang X; Qiang X; Li Y; Luo L; Xu R; Zheng Y; Cao Z; Tan Z; Deng Y
[Ad] Endereço:Department of Medicinal Chemistry, Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
[Ti] Título:Pyridoxine-resveratrol hybrids Mannich base derivatives as novel dual inhibitors of AChE and MAO-B with antioxidant and metal-chelating properties for the treatment of Alzheimer's disease.
[So] Source:Bioorg Chem;71:305-314, 2017 Apr.
[Is] ISSN:1090-2120
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A series of pyridoxine-resveratrol hybrids Mannich base derivatives as multifunctional agents have been designed, synthesized and evaluated for cholinesterase (ChE) and monoamine oxidase (MAO) inhibitory activity. To further explore the multifunctional properties of the new derivatives, their antioxidant activities and metal-chelating properties were also tested. The results showed that most of these compounds could selectively inhibit acetylcholinesterase (AChE) and MAO-B. Among them, compounds 7d and 8b exhibited the highest potency for AChE inhibition with IC values of 2.11µM and 1.56µM, respectively, and compound 7e exhibited the highest MAO-B inhibition with an IC value of 2.68µM. The inhibition kinetic analysis revealed that compound 7d showed a mixed-type inhibition, binding simultaneously to the CAS and PAS of AChE. Molecular modeling study was also performed to investigate the binding mode of these hybrids with MAO-B. In addition, all target compounds displayed good antioxidant and metal-chelating properties. Taken together, these preliminary findings can be a new starting point for further development of multifunctional agents for Alzheimer's disease.
[Mh] Termos MeSH primário: Antioxidantes/farmacologia
Quelantes/farmacologia
Inibidores da Colinesterase/farmacologia
Inibidores da Monoaminoxidase/farmacologia
Monoaminoxidase/metabolismo
Piridoxina/farmacologia
Estilbenos/farmacologia
[Mh] Termos MeSH secundário: Acetilcolinesterase/metabolismo
Doença de Alzheimer/tratamento farmacológico
Doença de Alzheimer/enzimologia
Animais
Antioxidantes/química
Quelantes/química
Inibidores da Colinesterase/química
Electrophorus
Seres Humanos
Cinética
Bases de Mannich/química
Bases de Mannich/farmacologia
Metais/metabolismo
Modelos Moleculares
Inibidores da Monoaminoxidase/química
Piridoxina/análogos & derivados
Ratos
Estilbenos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Chelating Agents); 0 (Cholinesterase Inhibitors); 0 (Mannich Bases); 0 (Metals); 0 (Monoamine Oxidase Inhibitors); 0 (Stilbenes); EC 1.4.3.4 (Monoamine Oxidase); EC 3.1.1.7 (Acetylcholinesterase); KV2JZ1BI6Z (Pyridoxine); Q369O8926L (resveratrol)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170606
[Lr] Data última revisão:
170606
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170308
[St] Status:MEDLINE


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[PMID]:28202327
[Au] Autor:Rybka S; Obniska J; Rapacz A; Filipek B; Zmudzki P
[Ad] Endereço:Department of Medicinal Chemistry, Faculty of Pharmacy, Jagiellonian University, Medical College, 9 Medyczna Street, 30-688 Kraków, Poland. Electronic address: rybka.sabina@gmail.com.
[Ti] Título:Synthesis and evaluation of anticonvulsant properties of new N-Mannich bases derived from pyrrolidine-2,5-dione and its 3-methyl-, 3-isopropyl, and 3-benzhydryl analogs.
[So] Source:Bioorg Med Chem Lett;27(6):1412-1415, 2017 03 15.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The aim of this paper was to describe the synthesis of a library of 28 new 1,3-substituted pyrrolidine-2,5-dione as potential anticonvulsant agents. The anticonvulsant activity was evaluated using three acute models of seizures in mice (MES-maximal electroshock, scPTZ-subcutaneous pentylenetetrazole, and 6Hz-psychomotor seizure tests). The neurotoxicity was determined by rotarod test. The most promising compound was found to be N-[{morpholin-1-yl}-methyl]-3-benzhydryl-pyrrolidine-2,5-dione (15), as it was active in the MES (ED =41.0mg/kg), scPTZ (ED =101.6kg/mg), and 6Hz (ED =45.42mg/kg) tests. This compound displayed more beneficial protection index (PI) than antiepileptic drugs such as ethosuximide, lacosamide and valproic acid. In vitro studies for compound 15 were conducted and provided information that its possible mechanism of action is related to blocking of the neuronal voltage-sensitive sodium (site 2) and L-type calcium channels.
[Mh] Termos MeSH primário: Anticonvulsivantes/síntese química
Anticonvulsivantes/uso terapêutico
Bases de Mannich/química
Pirrolidinas/síntese química
Pirrolidinas/farmacologia
Convulsões/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Camundongos
Pirrolidinas/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anticonvulsants); 0 (Mannich Bases); 0 (Pyrrolidines)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171124
[Lr] Data última revisão:
171124
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170217
[St] Status:MEDLINE


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[PMID]:28190652
[Au] Autor:Qin M; Yan S; Wang L; Zhang H; Tian Y; Zhao Y; Gong P
[Ad] Endereço:Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, 103 Wenhua Road, Shenyang 110016, PR China. Electronic address: qinmingze001@126.com.
[Ti] Título:Novel 6-methoxycarbonyl indolinones bearing a pyrrole Mannich base moiety as angiokinase inhibitors.
[So] Source:Bioorg Med Chem;25(6):1778-1786, 2017 Mar 15.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Inhibition of tumor angiogenesis through simultaneously disturbing vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) mediated signaling pathways is a well-established approach in intervention of tumor. A series of 6-methoxycarbonyl indolinones bearing a pyrrole Mannich base moiety were synthesized and evaluated as potent angiokinase inhibitors. Compound 8a demonstrated favorable enzymatic activity against all subtypes of VEGFR and PDGFR. Also, it potently suppressed proliferation of HT-29 cells by inducing apoptosis. Compound 8a has emerged as a promising lead compound for development of angiokinase inhibitors targeting VEGFR and PDGFR.
[Mh] Termos MeSH primário: Indóis/farmacologia
Bases de Mannich/química
Inibidores de Proteínas Quinases/farmacologia
Proteínas Quinases/efeitos dos fármacos
Pirróis/química
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Linhagem Celular Tumoral
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Indóis/química
Concentração Inibidora 50
Simulação de Acoplamento Molecular
Neovascularização Patológica/prevenção & controle
Receptor beta de Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores
Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Indoles); 0 (Mannich Bases); 0 (Protein Kinase Inhibitors); 0 (Pyrroles); 0 (Vascular Endothelial Growth Factor A); EC 2.7.- (Protein Kinases); EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170214
[St] Status:MEDLINE


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[PMID]:27951485
[Au] Autor:Li Y; Qiang X; Luo L; Yang X; Xiao G; Liu Q; Ai J; Tan Z; Deng Y
[Ad] Endereço:Department of Medicinal Chemistry, Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
[Ti] Título:Aurone Mannich base derivatives as promising multifunctional agents with acetylcholinesterase inhibition, anti-ß-amyloid aggragation and neuroprotective properties for the treatment of Alzheimer's disease.
[So] Source:Eur J Med Chem;126:762-775, 2017 Jan 27.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:A series of aurone Mannich base derivatives were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease. In vitro assays demonstrated that most of the derivatives were selective AChE inhibitors with good multifunctional properties. Among them, compound 7d exhibited outstanding inhibitory activity for RatAChE, EeAChE and HuAChE (IC = 0.00878 ± 0.0002 µM, 0.0212 ± 0.006 µM and 0.0371 ± 0.004 µM, respectively). Moreover, 7d displayed high antioxidant activity and could confer significant neuroprotective effect against H O -induced PC-12 cell injury. In addition, 7d also showed biometal chelating abilities, good self- and Cu -induced Aß aggregation inhibitory potency and high BBB permeability. These multifunctional properties highlight 7d as promising candidate for further studies directed to the development of novel drugs against AD.
[Mh] Termos MeSH primário: Doença de Alzheimer/tratamento farmacológico
Bases de Mannich/síntese química
[Mh] Termos MeSH secundário: Peptídeos beta-Amiloides/antagonistas & inibidores
Peptídeos beta-Amiloides/metabolismo
Animais
Barreira Hematoencefálica/efeitos dos fármacos
Inibidores da Colinesterase/síntese química
Inibidores da Colinesterase/farmacologia
Desenho de Drogas
Electrophorus
Seres Humanos
Bases de Mannich/farmacologia
Fármacos Neuroprotetores/síntese química
Fármacos Neuroprotetores/farmacologia
Células PC12
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amyloid beta-Peptides); 0 (Cholinesterase Inhibitors); 0 (Mannich Bases); 0 (Neuroprotective Agents)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170221
[Lr] Data última revisão:
170221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161213
[St] Status:MEDLINE


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[PMID]:27933733
[Au] Autor:Milosev MZ; Jakovljevic K; Joksovic MD; Stanojkovic T; Matic IZ; Perovic M; Tesic V; Kanazir S; Mladenovic M; Rodic MV; Leovac VM; Trifunovic S; Markovic V
[Ad] Endereço:Faculty of Medicinal Science, University of Kragujevac, Kragujevac, Serbia.
[Ti] Título:Mannich bases of 1,2,4-triazole-3-thione containing adamantane moiety: Synthesis, preliminary anticancer evaluation, and molecular modeling studies.
[So] Source:Chem Biol Drug Des;89(6):943-952, 2017 Jun.
[Is] ISSN:1747-0285
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A series of 18 novel N-Mannich bases derived from 5-adamantyl-1,2,4-triazole-3-thione was synthesized and characterized using NMR spectroscopy and X-ray diffraction technique. All derivatives were evaluated for their anticancer potential against four human cancer cell lines. Several tested compounds exerted good cytotoxic activities on K562 and HL-60 cell lines, along with pronounced selectivity, showing lower cytotoxicity against normal fibroblasts MRC-5 compared to cancer cells. The effects of compounds 5b, 5e, and 5j on the cell cycle were investigated by flow cytometric analysis. It was found that these compounds cause the accumulation of cells in the subG1 and G1 phases of the cell cycle and induce caspase-dependent apoptosis, while the anti-angiogenic effects of 5b, 5e, and 5j have been confirmed in EA.hy926 cells using a tube formation assay. Further, the interaction of Bax protein with compound 5b was investigated by means of molecular modeling, applying the combined molecular docking/molecular dynamics approach.
[Mh] Termos MeSH primário: Antineoplásicos/síntese química
Antineoplásicos/farmacologia
Simulação de Acoplamento Molecular
Tionas/química
Tionas/farmacologia
[Mh] Termos MeSH secundário: Adamantano/química
Adamantano/farmacologia
Antineoplásicos/química
Apoptose/efeitos dos fármacos
Ciclo Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Fibroblastos/efeitos dos fármacos
Seres Humanos
Concentração Inibidora 50
Bases de Mannich/química
Bases de Mannich/farmacologia
Estrutura Molecular
Tionas/síntese química
Triazóis/química
Triazóis/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Mannich Bases); 0 (Thiones); 0 (Triazoles); 288-88-0 (1,2,4-triazole); PJY633525U (Adamantane)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171103
[Lr] Data última revisão:
171103
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161210
[St] Status:MEDLINE
[do] DOI:10.1111/cbdd.12920


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[PMID]:27923535
[Au] Autor:Li Y; Qiang X; Luo L; Yang X; Xiao G; Zheng Y; Cao Z; Sang Z; Su F; Deng Y
[Ad] Endereço:Department of Medicinal Chemistry, Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
[Ti] Título:Multitarget drug design strategy against Alzheimer's disease: Homoisoflavonoid Mannich base derivatives serve as acetylcholinesterase and monoamine oxidase B dual inhibitors with multifunctional properties.
[So] Source:Bioorg Med Chem;25(2):714-726, 2017 Jan 15.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A series of homoisoflavonoid Mannich base derivatives were designed, synthesized and evaluated as multifunctional agents against Alzheimer's disease. It demonstrated that most of the derivatives were selective AChE and MAO-B dual inhibitors with good multifunctional properties. Among them, compound 10d displayed the comprehensive advantages, with excellent AChE and MAO-B inhibitory activities (IC =2.49±0.08nM and 1.74±0.0581µM, respectively), good self- and Cu -induced Aß aggregation inhibitory potency, antioxidant activity, biometal chelating ability and high BBB permeability. These multifunctional properties make 10d as an excellent candidate for the development of efficient drugs against AD.
[Mh] Termos MeSH primário: Doença de Alzheimer/tratamento farmacológico
Inibidores da Colinesterase/farmacologia
Desenho de Drogas
Isoflavonas/farmacologia
Inibidores da Monoaminoxidase/farmacologia
[Mh] Termos MeSH secundário: Acetilcolinesterase/metabolismo
Doença de Alzheimer/metabolismo
Inibidores da Colinesterase/síntese química
Relação Dose-Resposta a Droga
Seres Humanos
Isoflavonas/síntese química
Isoflavonas/química
Bases de Mannich/síntese química
Bases de Mannich/farmacologia
Simulação de Acoplamento Molecular
Estrutura Molecular
Monoaminoxidase/metabolismo
Inibidores da Monoaminoxidase/síntese química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cholinesterase Inhibitors); 0 (Isoflavones); 0 (Mannich Bases); 0 (Monoamine Oxidase Inhibitors); EC 1.4.3.4 (Monoamine Oxidase); EC 3.1.1.7 (Acetylcholinesterase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170814
[Lr] Data última revisão:
170814
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161208
[St] Status:MEDLINE


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[PMID]:27915183
[Au] Autor:Malawska K; Rak A; Gryzlo B; Salat K; Michalowska M; Zmudzka E; Lodarski K; Malawska B; Kulig K
[Ad] Endereço:Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9 St., 30-688 Kraków, Poland.
[Ti] Título:Search for new potential anticonvulsants with anxiolytic and antidepressant properties among derivatives of 4,4-diphenylpyrrolidin-2-one.
[So] Source:Pharmacol Rep;69(1):105-111, 2017 Feb.
[Is] ISSN:1734-1140
[Cp] País de publicação:Poland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The aim of this study was to synthesize a series of new N-Mannich bases derived from 4,4-diphenylpyrrolidin-2-one having differently substituted 4-phenylpiperazines as potential anticonvulsant agents with additional (beneficial) pharmacological properties. METHODS: The target compounds 8-12 were prepared in one step from the 4-substituted phenylpiperazines, paraformaldehyde, and synthesized 4,4-diphenylpyrrolodin-2-one (7) by a Mannich-type reaction. The obtained compounds were assessed and tested for their anticonvulsant activity in two screening mouse models of seizures, i.e., the maximal electroshock (MES) test and in the subcutaneous pentylenetetrazole (scPTZ) test. The effect of these compounds on animals' motor coordination was measured in the rotarod test. A selected 4,4-diphenyl-1-((4-phenylpiperazin-1-yl)methyl)pyrrolidin-2-one (8) was evaluated in vivo for its anxiolytic- and antidepressant-like properties. Its impact on animals' locomotor activity was also evaluated. RESULTS: Compound 8 showed protection (25%) in the MES and in the scPTZ tests at the dose of 100mg/kg and was not neurotoxic. In the four-plate test, compound 8 at the dose of 30mg/kg showed a statistically significant (p<0.05) anxiolytic-like activity. In the forced swim test, it reduced the immobility time by 24.3% (significant at p<0.05), which indicates its potential antidepressant-like properties. In the locomotor activity test, compound 8 significantly reduced animals' locomotor activity by 79.9%. CONCLUSION: The results obtained make a new derivative of 4,4-diphenyl-1-((4-phenylpiperazin-1-yl)methyl)pyrrolidin-2-one (8) a promising lead structure for further development.
[Mh] Termos MeSH primário: Ansiolíticos/química
Anticonvulsivantes/química
Antidepressivos/química
Piperazinas/química
[Mh] Termos MeSH secundário: Animais
Ansiolíticos/uso terapêutico
Anticonvulsivantes/uso terapêutico
Antidepressivos/uso terapêutico
Relação Dose-Resposta a Droga
Eletrochoque/efeitos adversos
Masculino
Bases de Mannich/química
Bases de Mannich/uso terapêutico
Camundongos
Pentilenotetrazol/toxicidade
Piperazinas/uso terapêutico
Convulsões/induzido quimicamente
Convulsões/tratamento farmacológico
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Anxiety Agents); 0 (Anticonvulsants); 0 (Antidepressive Agents); 0 (Mannich Bases); 0 (Piperazines); J9225CBI7D (phenylpiperazine); WM5Z385K7T (Pentylenetetrazole)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170323
[Lr] Data última revisão:
170323
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161205
[St] Status:MEDLINE


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[PMID]:27912173
[Au] Autor:Mahal K; Ahmad A; Schmitt F; Lockhauserbäumer J; Starz K; Pradhan R; Padhye S; Sarkar FH; Koko WS; Schobert R; Ersfeld K; Biersack B
[Ad] Endereço:Organic Chemistry Laboratory, University of Bayreuth, Universitaetsstrasse 30, 95440 Bayreuth, Germany.
[Ti] Título:Improved anticancer and antiparasitic activity of new lawsone Mannich bases.
[So] Source:Eur J Med Chem;126:421-431, 2017 Jan 27.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Substituted lawsone Mannich bases 2a-e, 3a-e and 4a-e were prepared and tested for their biological activities. The new fatty alkyl substituted compounds 2a-c exhibited strong and selective growth inhibitory activities in the low one-digit micromolar and sub-micromolar range against a panel of human cancer cell lines associated with ROS formation. In addition, compounds 2a-c revealed sub-micromolar anti-trypanosomal activities against parasitic Trypanosoma brucei brucei cells via deformation of the microtubule cytoskeleton. The N-hexadecyl compound 2c was also highly active against locally isolated Entamoeba histolytica parasite samples exceeding the activity of metronidazole.
[Mh] Termos MeSH primário: Antineoplásicos/química
Antineoplásicos/farmacologia
Bases de Mannich/química
Naftoquinonas/química
Naftoquinonas/farmacologia
Tripanossomicidas/química
Tripanossomicidas/farmacologia
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Citoesqueleto/efeitos dos fármacos
Citoesqueleto/metabolismo
Desenho de Drogas
Entamoeba histolytica/efeitos dos fármacos
Seres Humanos
Concentração Inibidora 50
Relação Estrutura-Atividade
Trypanosoma brucei brucei/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Mannich Bases); 0 (Naphthoquinones); 0 (Trypanocidal Agents); TLH4A6LV1W (lawsone)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170222
[Lr] Data última revisão:
170222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161203
[St] Status:MEDLINE



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