Quantitative structure-activity relationships (QSAR) of 4-amino-2,6-diarylpyrimidine-5-carbonitriles with anti-inflammatory activity

Silva, João Bosco P. da; Ramos, Mozart N.; Neto, Benício de Barros; Melo, Sebastião J. de; Falcão, Emerson Peter da Silva; Catanho, Maria Teresa Jansen de Almeida

doi:10.1590/s0103-50532008000200021

Cited by 8 publications

(3 citation statements)

References 9 publications

(13 reference statements)

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“…Injections of free 4-aminopyrimidine-bis-substituted solutions and encapsulated in liposomes at a dose equivalent to 15 mg/Kg of body weight, 5-FU (positive control) at a dose of 20 mg/Kg and weight-dependent placebos (saline) were given intraperitoneally. The therapeutic doses were studied previously (Da Silva et al 2008, Falcão et al 2006) The 4-amino-pyrimidine-bis-substituted compound was dissolved in a solution of 2.5% Tween 80 in sterile 0.9% NaCl solution.…”

Section: Experimental Animalsmentioning

confidence: 99%

4-amino-2-phenyl-6-(p-fluorophenyl)-5-carbonitrile-pyrimidine-bis-substituted-loaded liposomes as promising system for cancer treatment

Oliveira

Almeida

Nogueira

et al. 2023

An. Acad. Bras. Ciênc.

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The aim of the present study was to perform in vitro and in vivo assessments of the antineoplastic action of 4-amino-pyrimidine encapsulated in liposomes.Liposomes were prepared and characterized for particle size and drug encapsulation and submitted to long-term stability tests. Cytotoxicity assays were performed in HeLa cells. Antineoplastic activity was investigated using the experimental sarcoma 180 tumor in Swiss albino mice. Encapsulation efficiency was 82.93 ± 0.04% and no significant changes were found with respect to particle size or pH after centrifugation and mechanical agitation tests. The in vitro results at concentration of 20 μg/mL indicated a considerable reduction in cell viability after treatment with encapsulated pyrimidine (75.91%). The in vivo assays using the compounds in encapsulated and free forms and 5-fluorouracil achieved tumor inhibition rates of 66.47 ± 26.8%, 50.46 ± 16.24% and 14.47 ± 9.22%, respectively. Mitotic counts demonstrated a greater reduction in the number of mitoses in animals treated with liposomal pyrimidine (32.15%) compared to those treated with the pyrimidine free (87.69%) and 5-fluorouracil (71.39%). This study demonstrated that the development of liposome formulations containing 4-aminopyrimidine is a promising alternative for overcoming limitations related to the toxicity of current cancer treatment, ensuring greater therapeutic efficacy.

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Section: Experimental Animalsmentioning

confidence: 99%

4-amino-2-phenyl-6-(p-fluorophenyl)-5-carbonitrile-pyrimidine-bis-substituted-loaded liposomes as promising system for cancer treatment

Oliveira

Almeida

Nogueira

et al. 2023

An. Acad. Bras. Ciênc.

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“…We consider that, being the first data set of the class, the objective would be to generate a model that would allow an initial rationalization and prediction of new analogues. 20,21 The standard deviations of predicted values (s), Standard Deviation of Predictor Errors Sum of Squares (SPRESS) and correlation matrix between descriptors were also considered as validation procedures. Additionally, leave-n-out validations and Yscrambling were performed.…”

Section: Molecular Structures and Geometry Optimizationsmentioning

confidence: 99%

Quantitative Structure-Activity Relationship (QSAR) Study of Resveratrol-Oxadiazole Hybrids with Antiproliferative Activity in Breast Cancer Cells

Santos

Brito²,

Silva³

et al. 2019

Rev. Virtual Quim.

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Estudo da Relação Quantitativa Estrutura-Atividade (QSAR) de Híbridos Resveratrol-Oxadiazóis com Atividade Antiproliferativa em Células do Câncer de Mama Resumo: Produtos naturais são uma fonte inesgotável de novos compostos bioativos. Polifenóis contendo a porção estilbeno estão presentes em várias espécies vegetais, possuindo um conhecido potencial quimioterapêutico com baixa toxicidade. Dentre estes, destaca-se o resveratrol, um composto abundante na uva e no vinho tinto que tem apresentado atividades promissoras contra vários tipos de linhagens de células tumorais, sendo assim um bom ponto de partida para o desenho de novos fármacos. Nas estratégias modernas de desenho de drogas, o estabelecimento de relações quantitativas entre a estrutura química e a atividade biológica é parte crucial. Neste estudo, apresentamos um estudo QSAR inicial baseado em híbridos resveratrol-oxadiazóis previamente sintetizados, com atividade contra células do câncer de mama, identificando descritores moleculares que podem ser úteis para proposições qualitativas e avaliações quantitativas de análogos mais ativos.

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“…Because of the aforementioned pharmacological potential of this class of compounds, our group has been involved in synthesizing and testing the pharmacological activities of pyrimidinone and pyrimidine derivatives, for the purposes of drug discovery and development [ 17 , 18 , 19 , 24 , 27 , 33 , 34 , 35 ]. Recently, we have synthesized and evaluated the acute toxicity, and anti-edematogenic and antinociceptive activities of 3,4-dihydro-2-phenyl-6- para -fluorophenyl-4-oxo-pyrimidine-5-carbo-nitrile, a prototype for this class of compounds, which has shown promising pharmacological activities and low toxicity [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Comparative Computational Studies of 3,4-Dihydro-2,6-diaryl-4-oxo-pyrimidine-5-carbonitrile Derivatives as Potential Antinociceptive Agents

et al. 2012

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In this study, the antinociceptive properties of 3,4-dihydro-2,6-diaryl-4-oxo-pyrimidine-5-carbonitrile derivatives 5a–i at doses of 25 and 50 mg/kg were evaluated in mice, using the abdominal constriction test. Molecular modeling studies were also performed using density functional theory calculations. These data provided information about the electrostatic and ionization potentials and were used to compare the antinociceptive activity of the title compounds. The most active compounds were 3,4-dihydro-2-(4-chlorophenyl)-6-(4-methoxyphenyl)-4-oxo-pyrimidine-5-carbonitrile (5b) and 3,4-dihydro-2,6-diphenyl-4-oxo-pyrimidine-5-carbonitrile (5i), which inhibited the number of abdominal constrictions, at 50 mg/kg dose, in 88.6% and 88% of the sample, respectively. A preliminary SAR study demonstrated that halogen replacement in the phenyl rings of the compounds under study reduces the antinociceptive activity. DFT calculations showed that there is a high correlation between the ionization potentials and the analgesic properties of the compounds. It was found that compounds with a positive ionization potential (compounds 5b and 5i) were found to be the best analgesic drugs in this series.

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Quantitative structure-activity relationships (QSAR) of 4-amino-2,6-diarylpyrimidine-5-carbonitriles with anti-inflammatory activity

Cited by 8 publications

References 9 publications

4-amino-2-phenyl-6-(p-fluorophenyl)-5-carbonitrile-pyrimidine-bis-substituted-loaded liposomes as promising system for cancer treatment

4-amino-2-phenyl-6-(p-fluorophenyl)-5-carbonitrile-pyrimidine-bis-substituted-loaded liposomes as promising system for cancer treatment

Quantitative Structure-Activity Relationship (QSAR) Study of Resveratrol-Oxadiazole Hybrids with Antiproliferative Activity in Breast Cancer Cells

Comparative Computational Studies of 3,4-Dihydro-2,6-diaryl-4-oxo-pyrimidine-5-carbonitrile Derivatives as Potential Antinociceptive Agents

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