Base de dados : MEDLINE
Pesquisa : D03.132.032 [Categoria DeCS]
Referências encontradas : 207 [refinar]
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[PMID]:28886509
[Au] Autor:Murahari M; Prakash KV; Peters GJ; Mayur YC
[Ad] Endereço:Department of Pharmaceutical Chemistry, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Mumbai 400 056, India.
[Ti] Título:Acridone-pyrimidine hybrids- design, synthesis, cytotoxicity studies in resistant and sensitive cancer cells and molecular docking studies.
[So] Source:Eur J Med Chem;139:961-981, 2017 Oct 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Hybrid systems of acridones with substituted pyrimidines were designed with an objective of discovering next generation anticancer agents targeting multiple mechanisms in the cancer cell. Hybrid compounds were synthesized by simple and convenient methods in the lab, characterized by NMR and Mass spectral methods and screened for cytotoxicity against A549 (lung), Hela (cervical), MCF7 (breast) and MDA-MB-231 (breast) cancer cell lines respectively. Evaluation of compounds for cell proliferation identified active compounds 11b, 11d and 11h against MCF7, MDA-MB-231 and A549 cell lines. Further absorption titrations with CT-DNA and gel electrophoresis identified that hybrid molecules displayed anticancer activity partly by DNA intercalation. Also further results of western blotting assay with Akt kinase identified that hybrid compounds have the ability to inhibit the Akt kinase activity and induce apoptosis, with ABCC1 suggests that active compounds too have the ability to modulate multidrug resistance (MDR) associated with ABCC1/MRP1. Selective Akt1 kinase assay have identified 11a, 11b, 11d and 11h as potential inhibitors. Molecular docking studies identified the orientation and binding interactions at the active site of Akt1 and DNA. Compounds 12e and 12f have shown good cytotoxicity profile against lung cancer cell lines of sensitive and resistant type. Acute toxicity study of compound 12f at the dose of 5000 mg/kg has identified no signs of clinical toxicity. Prediction of ADMET properties and oral toxicity of the drug likeness features of new hybrid systems were carried out using software's. This experimental data suggests that hybrid systems of acridone with substituted pyrimidines can be taken as a lead for the design of efficient inhibitors and active compounds which can be taken up for further studies.
[Mh] Termos MeSH primário: Acridonas/farmacologia
Antineoplásicos/farmacologia
Desenho de Drogas
Simulação de Acoplamento Molecular
Pirimidinas/farmacologia
[Mh] Termos MeSH secundário: Acridonas/química
Antineoplásicos/síntese química
Antineoplásicos/química
Apoptose/efeitos dos fármacos
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Estrutura Molecular
Pirimidinas/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acridones); 0 (Antineoplastic Agents); 0 (Pyrimidines); 6BK306GUQA (acridone); K8CXK5Q32L (pyrimidine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170909
[St] Status:MEDLINE


  2 / 207 MEDLINE  
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Rahal, Paula
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[PMID]:28699869
[Au] Autor:Campos GRF; Bittar C; Jardim ACG; Shimizu JF; Batista MN; Paganini ER; Assis LR; Bartlett C; Harris M; Bolzani VDS; Regasini LO; Rahal P
[Ad] Endereço:1​Institute of Bioscience, Language and Exact Science, IBILCE, UNESP - São Paulo State University, São José do Rio Preto, SP, Brazil.
[Ti] Título:Hepatitis C virus in vitro replication is efficiently inhibited by acridone Fac4.
[So] Source:J Gen Virol;98(7):1693-1701, 2017 Jul.
[Is] ISSN:1465-2099
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Hepatitis C virus (HCV) affects about 170 million people worldwide. The current treatment has a high cost and variable response rates according to the virus genotype. Acridones, a group of compounds extracted from natural sources, showed potential antiviral actions against HCV. Thus, this study aimed to evaluate the effect of a panel of 14 synthetic acridones on the HCV life cycle. The compounds were screened using an Huh7.5 cell line stably harbouring the HCV genotype 2a subgenomic replicon SGR-Feo-JFH-1. Cells were incubated in the presence or absence of compounds for 72 h and cell viability and replication levels were assessed by MTT and luciferase assays, respectively. At a concentration of 5 µM the acridone Fac4 exhibited a >90 % inhibition of HCV replication with no effect on cell viability. The effects of Fac4 on virus replication, entry and release steps were evaluated in Huh7.5 cells infected with the JFH-1 isolate of HCV (HCVcc). Fac4 inhibited JFH-1 replication to approximately 70 %, while no effect was observed on virus entry. The antiviral activity of Fac4 was also observed on viral release, with almost 80 % of inhibition. No inhibitory effect was observed against genotype 3 replication. Fac4 was able to intercalate into dsRNA, however did not inhibit NS5B polymerase activity or translation driven by the HCV IRES. Although its mode of action is partly understood, Fac4 presents significant inhibition of HCV replication and can therefore be considered as a candidate for the development of a future anti-HCV treatment.
[Mh] Termos MeSH primário: Acridonas/farmacologia
Antivirais/farmacologia
Hepacivirus/efeitos dos fármacos
Hepacivirus/fisiologia
Replicação Viral/efeitos dos fármacos
[Mh] Termos MeSH secundário: Acridonas/síntese química
Antivirais/síntese química
Genoma Viral/efeitos dos fármacos
Hepacivirus/genética
Hepatite C/virologia
Seres Humanos
Replicon/efeitos dos fármacos
Internalização do Vírus/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acridones); 0 (Antiviral Agents)
[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:170713
[St] Status:MEDLINE
[do] DOI:10.1099/jgv.0.000808


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[PMID]:28246041
[Au] Autor:Murahari M; Kharkar PS; Lonikar N; Mayur YC
[Ad] Endereço:Department of Pharmaceutical Chemistry, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Mumbai 400 056, India; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, Bangalore 560 054, India.
[Ti] Título:Design, synthesis, biological evaluation, molecular docking and QSAR studies of 2,4-dimethylacridones as anticancer agents.
[So] Source:Eur J Med Chem;130:154-170, 2017 Apr 21.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Drug resistance in cancer is an unmet medical challenge and a major drawback for the failure of many chemotherapeutic drugs. Search for targeted, effective drug with minimum toxicity is an urgent need. Acridone which is an alkaloid derivative has been attributed as molecule in reversing drug resistance in cancer cells for a long time now. In the present investigation, an attempt has been made to explore the chemosensitizing ability of 2,4-dimethylacridones with alkyl side chain containing terminally substituted tertiary amino groups. Considering the structural features required for the MDR reversal activity, acridone derivatives have been synthesized with propyl and butyl side chain containing morpholinyl, piperidinyl, N-methylpiperazinyl, N,N-diethylamino, N-diethanolamino, N-[(ß-hydroxylethyl)]piperazino at the terminus of the alkyl side chain. cLogP values for the synthesized compounds ranged from 2.96 to 4.72 for the propyl derivatives and 3.41 to 5.15 for the butyl derivatives. All the compounds were screened against breast cancer sensitive MCF7 and resistant MCF7/ADR cell lines. Compounds 12e and 12f have shown better cytotoxicity profiles with IC of 4 ± 0.05 and 2 ± 0.03 µM against MCF7 cells, 5.21 ± 0.13 and 2.56 ± 0.05 µM against MCF7/ADR cells. Photolabelling studies with [ H]-azidopine and molecular docking studies have identified that 2,4-dimethylacridones have potential to modulate the P-gp mediated multidrug resistance. Docking studies identified that compounds have shown favorable interactions with P-gp. QSAR equation was derived for cytotoxicity vs molecular descriptors of acridone derivatives. Best models with good predictive ability have been generated with very high square correlation coefficient (R ) values of 0.889, 0.964 and 0.983.
[Mh] Termos MeSH primário: Acridonas/química
Antineoplásicos/química
Relação Quantitativa Estrutura-Atividade
[Mh] Termos MeSH secundário: Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo
Acridonas/farmacologia
Antineoplásicos/síntese química
Antineoplásicos/farmacologia
Linhagem Celular Tumoral
Desenho de Drogas
Resistência a Múltiplos Medicamentos/efeitos dos fármacos
Resistência a Medicamentos Antineoplásicos/efeitos dos fármacos
Seres Humanos
Simulação de Acoplamento Molecular
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ATP-Binding Cassette, Sub-Family B, Member 1); 0 (Acridones); 0 (Antineoplastic Agents); 6BK306GUQA (acridone)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170302
[St] Status:MEDLINE


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[PMID]:28237663
[Au] Autor:Zhang B; Wang N; Zhang C; Gao C; Zhang W; Chen K; Wu W; Chen Y; Tan C; Liu F; Jiang Y
[Ad] Endereço:Department of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, PR China; Shenzhen Kivita Innovative Drug Discovery Institute, Shenzhen, 518057, PR China.
[Ti] Título:Novel multi-substituted benzyl acridone derivatives as survivin inhibitors for hepatocellular carcinoma treatment.
[So] Source:Eur J Med Chem;129:337-348, 2017 Mar 31.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Sorafenib was the only small-molecule drug approved by FDA for treatment of the advanced hepatocellular carcinoma (HCC). Recent study indicated that YM155 was a promising agent for HCC cells with high survivin expression, however, the antitumor activity needs to be further improved. Based on molecular docking and rational design method, a series of multi-substituted benzyl acridone derivatives were designed and synthesized. MTT assay indicated that some of the synthesized compounds displayed better antiproliferative activity against HepG2 cells than YM155. Later study indicated that the representive compound 8u may directly interact with survivin protein and induce HepG2 cells apoptosis, which is different from YM155. In addition, ADME property was predicted in silico, and it performed well. Moreover, in vivo preliminary experiments showed that 8u may be a good lead compound in the treatment of HCC.
[Mh] Termos MeSH primário: Acridonas/síntese química
Antineoplásicos/síntese química
Carcinoma Hepatocelular/tratamento farmacológico
Proteínas Inibidoras de Apoptose/antagonistas & inibidores
Neoplasias Hepáticas/tratamento farmacológico
[Mh] Termos MeSH secundário: Acridonas/farmacologia
Antineoplásicos/farmacologia
Apoptose/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Desenho de Drogas
Células Hep G2
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acridones); 0 (Antineoplastic Agents); 0 (BIRC5 protein, human); 0 (Inhibitor of Apoptosis Proteins)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170309
[Lr] Data última revisão:
170309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170227
[St] Status:MEDLINE


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[PMID]:28092865
[Au] Autor:Iwaszkiewicz-Grzes D; Cholewinski G; Kot-Wasik A; Trzonkowski P; Dzierzbicka K
[Ad] Endereço:Department of Organic Chemistry, Gdansk University of Technology, ul. G. Narutowicza 11/12, 80-233 Gdansk, Poland; Department of Clinical Immunology and Transplantology, Medical University of Gdansk, ul. Debinki 7, 80-211 Gdansk, Poland.
[Ti] Título:Investigations on the immunosuppressive activity of derivatives of mycophenolic acid in immature dendritic cells.
[So] Source:Int Immunopharmacol;44:137-142, 2017 Mar.
[Is] ISSN:1878-1705
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The main activity of mycophenolic acid 1 (MPA) and its analogs is the inhibition of proliferation of T cells. Here, we hypothesized that MPA and its conjugates inhibits also the activity of antigen-presenting cells (APC) including dendritic cells (DCs). We tested the effect of novel amino acid derivatives of MPA and conjugates of MPA with acridines/acridones on DCs by flow cytometry, ELISA and MLR assay. Both acridines/acridone derivatives could inhibit the maturation of DC, as shown by the decreased expression of B7 family receptors. It was confirmed in the mixed leucocyte reaction (MLR), in which T cells challenged with DCs pretreated with the analogs showed decreased proliferation and reduced cytokine secretion. The most interesting activity in this series of studies, that is, the suppression of CD86 receptor expression, decreased cytokine production and suppressed mixed leucocyte reaction, exhibited (mycophenoyl-N-3-propyl)-9-acridone-4-carboxamide ester 5a and (mycophenoyl-N-5-pentyl)-9-acridone-4-carboxamide ester 5b. These compounds reduced also the secretion of IL-2 and IL-15. In addition, they increased secretion of suppressive IL-10. Equally promising results were obtained for the N-mycophenoyl-D-glutamic acid 4b, which previously gave the highest value of selectivity. Acridone derivatives of MPA are therefore good immunosuppressive drug candidates for further testing.
[Mh] Termos MeSH primário: Doenças Autoimunes/tratamento farmacológico
Células Dendríticas/efeitos dos fármacos
Rejeição de Enxerto/tratamento farmacológico
Imunossupressores/farmacologia
Ácido Micofenólico/farmacologia
Transplante de Órgãos
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Acridonas/química
Antígeno B7-2/genética
Antígeno B7-2/metabolismo
Diferenciação Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Células Cultivadas
Células Dendríticas/imunologia
Seres Humanos
Interleucina-10/metabolismo
Interleucina-2/metabolismo
Ativação Linfocitária/efeitos dos fármacos
Teste de Cultura Mista de Linfócitos
Ácido Micofenólico/análogos & derivados
Ácido Micofenólico/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acridones); 0 (B7-2 Antigen); 0 (IL10 protein, human); 0 (Immunosuppressive Agents); 0 (Interleukin-2); 130068-27-8 (Interleukin-10); HU9DX48N0T (Mycophenolic Acid)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170117
[St] Status:MEDLINE


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[PMID]:27717196
[Au] Autor:Wang Y; Park D; Galermo AG; Gao D; Liu H; Lebrilla CB
[Ad] Endereço:Department of Chemistry, Tsinghua University, Beijing, P. R. China.
[Ti] Título:Changes in cellular glycosylation of leukemia cells upon treatment with acridone derivatives yield insight into drug action.
[So] Source:Proteomics;16(23):2977-2988, 2016 Dec.
[Is] ISSN:1615-9861
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:A new acridone derivative 2-aminoacetamido-10-(3, 5-dimethoxy)-benzyl-9(10H)-acridone hydrochloride (8a) has been shown to have potent antitumor activity. In order to understand the underlying action mechanism of 8a, three compounds of the same class with structures optimized step-by-step, 9(10H)-acridone (A), 10-(3,5-dimethoxy) benzyl-9(10H)-acridone (I) and 8a, were exposed to CCRF-CEM leukemia cell to determine the N-glycosylation changes using the microfluidic HPLC-chip-TOF MS platform. N-Glycans from whole cell lysates (WCL) and cell membranes (CM) were analyzed using isomer-sensitive chip-based porous graphitized carbon nano-LC/MS. A total of 223 N-glycan compositions and 398 N-glycan compounds were identified. Comparison of the two analyses showed that more apparent changes were observed in the CM compared with WCL, suggesting that CM may be a more sensitive indicator of changes in glycosylation. Upon 8a exposure to CCRF-CEM cells, a significant decrease in high-mannose-type glycans was observed. Different expressions of oligosaccharyltransferase subunits appear to play a key functional role in regulating the hypoglycosylation and contribute to the action mechanism of 8a. Taken together our findings suggest that glycosylation is strongly affected by therapeutic potency and can be used as possible biomarkers for monitoring toxicity and antitumor activity of 8a.
[Mh] Termos MeSH primário: Acridonas/farmacologia
Leucemia/tratamento farmacológico
Leucemia/metabolismo
Polissacarídeos/análise
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Glicômica/instrumentação
Glicômica/métodos
Glicosilação/efeitos dos fármacos
Hexosiltransferases/antagonistas & inibidores
Hexosiltransferases/metabolismo
Seres Humanos
Leucemia/patologia
Proteínas de Membrana/antagonistas & inibidores
Proteínas de Membrana/metabolismo
Modelos Teóricos
Polissacarídeos/química
Proteômica/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (2-aminoacetamido-10-(3, 5-dimethoxy)benzyl-9(10H)-acridone); 0 (Acridones); 0 (Membrane Proteins); 0 (Polysaccharides); EC 2.4.1.- (Hexosyltransferases); EC 2.4.99.18 (STT3A protein, human); EC 2.4.99.18 (STT3B protein, human)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170912
[Lr] Data última revisão:
170912
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161008
[St] Status:MEDLINE
[do] DOI:10.1002/pmic.201600218


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[PMID]:27295412
[Au] Autor:Parveen M; Aslam A; Nami SA; Malla AM; Alam M; Lee DU; Rehman S; Silva PS; Silva MR
[Ad] Endereço:Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India. Electronic address: mehtab.organic2009@gmail.com.
[Ti] Título:Potent acetylcholinesterase inhibitors: Synthesis, biological assay and docking study of nitro acridone derivatives.
[So] Source:J Photochem Photobiol B;161:304-11, 2016 Aug.
[Is] ISSN:1873-2682
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:The reaction of o-halobenzoic acid with aniline derivatives and their subsequent cyclization reaction yielded the acridone derivatives. The series of nitro acridone derivatives were prepared by Ullmann condensation in presence of copper as catalyst and were characterized by FTIR, (1)H, (13)C NMR and mass spectra. The structure of 5-nitro-(2-phenyl amino) benzoic acid (4) was confirmed by X-ray crystallography and was found to crystallize in P21/c space group. The in vitro efficacy of the compounds for their acetylcholinesterase (AChE) and antimicrobial inhibitory activities have been evaluated against the standard drugs Ampicillin and Gentamicin against Gram positive and Gram negative bacteria. 1,7-Dinitroacridone was found to be the most potent AChE inhibitor (IC50=0.22µM). Moreover, the compounds have been screened for their antioxidant activity using the DPPH assay. Also, docking study results were found to be in good agreement with the results obtained through in vitro experiments. The docking study further predicted possible binding conformation.
[Mh] Termos MeSH primário: Acridonas/química
Inibidores da Colinesterase/síntese química
[Mh] Termos MeSH secundário: Acetilcolinesterase/química
Acetilcolinesterase/metabolismo
Acridonas/metabolismo
Acridonas/farmacologia
Ampicilina/farmacologia
Antibacterianos/farmacologia
Ácido Benzoico/química
Sítios de Ligação
Inibidores da Colinesterase/metabolismo
Inibidores da Colinesterase/farmacologia
Cristalografia por Raios X
Bactérias Gram-Negativas/efeitos dos fármacos
Bactérias Gram-Positivas/efeitos dos fármacos
Espectroscopia de Ressonância Magnética
Conformação Molecular
Simulação de Acoplamento Molecular
Estrutura Terciária de Proteína
Espectroscopia de Infravermelho com Transformada de Fourier
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acridones); 0 (Anti-Bacterial Agents); 0 (Cholinesterase Inhibitors); 6BK306GUQA (acridone); 7C782967RD (Ampicillin); 8SKN0B0MIM (Benzoic Acid); EC 3.1.1.7 (Acetylcholinesterase)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170313
[Lr] Data última revisão:
170313
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160614
[St] Status:MEDLINE


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[PMID]:27272785
[Au] Autor:Schelz Z; Ocsovszki I; Bózsity N; Hohmann J; Zupkó I
[Ad] Endereço:Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary.
[Ti] Título:Antiproliferative Effects of Various Furanoacridones Isolated from Ruta graveolens on Human Breast Cancer Cell Lines.
[So] Source:Anticancer Res;36(6):2751-8, 2016 Jun.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIM: Thanks to its biologically active constituents, Ruta graveolens L. (Rutaceae) is a widely used medicinal plant. In our study, six furanoacridone alkaloids isolated from Ruta graveolens were investigated for their antiproliferative and pro-apoptotic effects on human breast cancer cell lines (MCF-7, MDA-MB-361, MDA-MB-231 and T47D). MATERIALS AND METHODS: The cell lines were pretreated with alkaloid components (rutacridone, isogravacridone chlorine (IGC), gravacridonediol monomethyl ether, gravacridonediol, gravacridonetriol, a 1:1 mixture of gravacridonetriol and - diol monoglucosides) and their antiproliferative effects were determined by the MTT assay. RESULTS: IGC had the most marked effect on cell proliferation of MDA-MB-231 (half maximal inhibitory concentration (IC50)=2.27 µM). Cell-cycle analysis was applied to quantify the effect of IGC on subpopulations of MDA-MB-231 and MCF-7 cells. It caused a cell-cycle disturbance by decreasing the G2/M and G0/G1 and increasing the S phase and the appearance of the subdiploid (sub-G1) population. Hoechst 33258-propidium iodide staining was used to evaluate the morphological changes in IGC-pretreated MDA-MB-231 and MCF-7 cells, revealing the appearance of apoptotic features. IGC was found to cause a modest activation of caspase-3 and -9, but not caspase-8, indicating the activation of an intrinsic apoptotic pathway in MDA-MB-231 cells. CONCLUSIONS: These in vitro findings indicate that furanoacridones are suitable candidates for anticancer drug development.
[Mh] Termos MeSH primário: Acridonas/farmacologia
Antineoplásicos Fitogênicos/farmacologia
Ruta/química
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Caspases/metabolismo
Ciclo Celular/efeitos dos fármacos
Feminino
Seres Humanos
Células MCF-7
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acridones); 0 (Antineoplastic Agents, Phytogenic); 6BK306GUQA (acridone); EC 3.4.22.- (Caspases)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170126
[Lr] Data última revisão:
170126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160609
[St] Status:MEDLINE


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[PMID]:26890115
[Au] Autor:Mohammadi-Khanaposhtani M; Shabani M; Faizi M; Aghaei I; Jahani R; Sharafi Z; Shamsaei Zafarghandi N; Mahdavi M; Akbarzadeh T; Emami S; Shafiee A; Foroumadi A
[Ad] Endereço:Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
[Ti] Título:Design, synthesis, pharmacological evaluation, and docking study of new acridone-based 1,2,4-oxadiazoles as potential anticonvulsant agents.
[So] Source:Eur J Med Chem;112:91-98, 2016 Apr 13.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:A number of acridone-based oxadiazoles 11a-n have been synthesized and evaluated for their anticonvulsant activity against pentylenetetrazole (PTZ)- and maximal electroshock (MES)-induced seizures in mice. Also, their neurotoxicity was evaluated by the rotarod test. Most of the compounds exhibited better anticonvulsant activity and higher safety respect to the standard drug, phenobarbital. Among the tested derivatives, compounds 11l with ED50 value of 2.08 mg/kg was the most potent compound in the PTZ test. The anticonvulsant effect of compound 11l was blocked by flumazenil, suggesting the involvement of benzodiazepine (BZD) receptors in the anticonvulsant activity of prototype compound 11l. Also, docking study of compound 11l in the BZD-binding site of GABAA receptor confirms possible binding of compound 11l with BZD receptors.
[Mh] Termos MeSH primário: Acridinas/química
Acridinas/uso terapêutico
Anticonvulsivantes/química
Anticonvulsivantes/uso terapêutico
Oxidiazóis/química
Oxidiazóis/uso terapêutico
Convulsões/tratamento farmacológico
[Mh] Termos MeSH secundário: Acridinas/farmacologia
Acridonas
Animais
Anticonvulsivantes/farmacologia
Eletrochoque
Camundongos
Simulação de Acoplamento Molecular
Oxidiazóis/farmacologia
Pentilenotetrazol
Receptores de GABA-A/metabolismo
Convulsões/induzido quimicamente
Convulsões/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Acridines); 0 (Acridones); 0 (Anticonvulsants); 0 (Oxadiazoles); 0 (Receptors, GABA-A); 6BK306GUQA (acridone); WM5Z385K7T (Pentylenetetrazole)
[Em] Mês de entrada:1611
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160219
[St] Status:MEDLINE


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[PMID]:26867676
[Au] Autor:Wang Y; Gao D; Chu B; Gao C; Cao D; Liu H; Jiang Y
[Ad] Endereço:Department of Chemistry, Tsinghua University, Beijing, P. R. China.
[Ti] Título:Exposure of CCRF-CEM cells to acridone derivative 8a triggers tumor death via multiple mechanisms.
[So] Source:Proteomics;16(7):1177-90, 2016 Apr.
[Is] ISSN:1615-9861
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:A newly synthesized acridone derivative 8a shows potent antitumor activity against CCRF-CEM leukemia cells. Herein, the first proteomic study of 8a effects in CCRF-CEM cells was performed by 2D nano-LC-ESI-MS/MS to better understand the mechanisms of action of 8a. Data analyses based on PLGS, STRING, Cytoscape, and database for annotation, visualization, and integrated discovery identified 55 proteins that were differentially expressed in response to 8a exposure. Multiple cellular pathways were affected, including chromatin organization, energy metabolism, DNA repair, oxidative-stress, and apoptosis. The changes in protein expression were further verified for PKM2. Moreover, 8a lowered down the expression of HEX and PFK-1. Lactate production was decreased in 8a-treated cells, indicating suppression of glycolysis. The elevated XRCC6 and decreased histone expression levels suggested increased DNA damage in 8a-treated cells, which was confirmed by the increased γ-H2AX foci. Molecular docking of 8a with DNA demonstrated direct interactions of 8a with DNA through three hydrogen bonds and four π-π interactions, potentially explaining the mode of action that 8a damaged to DNA. The differential protein profiling and dysfunction of metabolic pathways induced by 8a provide novel insights into the potential action mechanisms of 8a.
[Mh] Termos MeSH primário: Acridonas/toxicidade
Apoptose/efeitos dos fármacos
Estresse Oxidativo/efeitos dos fármacos
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Dano ao DNA/efeitos dos fármacos
Eletroforese em Gel Bidimensional
Metabolismo Energético/efeitos dos fármacos
Seres Humanos
Espectrometria de Massas
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Acridones); 6BK306GUQA (acridone)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160213
[St] Status:MEDLINE
[do] DOI:10.1002/pmic.201500317



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