رسالة جامعية
Molecular docking of Indolin-2-one compounds as promising dual aurora B/FLT3 inhibitors as anticancer agents ; Ancoramento molecular de compostos Indolin-2-ona como promissores inibidores duais de aurora B/FLT3 como agentes anticâncer
| العنوان: | Molecular docking of Indolin-2-one compounds as promising dual aurora B/FLT3 inhibitors as anticancer agents ; Ancoramento molecular de compostos Indolin-2-ona como promissores inibidores duais de aurora B/FLT3 como agentes anticâncer |
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| المؤلفون: | Fernandes, Italo Antônio |
| المساهمون: | Cunha, Elaine Fontes Ferreira da, Ramalho, Teodorico de Castro, Pereira, Luciana Lopes Silva, Alves, Fernando Henrique Ferrari, Ferrari, Fernando Henrique |
| بيانات النشر: | Universidade Federal de Lavras Programa de Pós-Graduação em Agroquímica UFLA brasil Departamento de Química |
| سنة النشر: | 2018 |
| المجموعة: | Repositório Institucional da Universidade Federal de Lavras (RIUFLA) |
| مصطلحات موضوعية: | Inibidores de aurora B quinase, Inibidores de FLT3, Derivados indolin-2-ona, Inibidores duais aurora B/FLT3, Leucemia mieloide aguda, Química medicinal, Compostos anticâncer, Química computacional, Ancoramento molecular, Aurora B kinase inhibitors, FLT3 inhibitors, Indolin-2-one derivatives, Dual aurora B/FLT3 inhibitors, Acute myeloid leukemia, Medicinal chemistry, Anticancer compounds, Computational chemistry, Docking, Química |
| الوصف: | Aurora kinase enzymes perform important roles in mammals, mainly in cell cycle. Overexpression of these enzymes is related to tumor development and indicative of worsening of clinical conditions of diagnosed patients with cancer. Aurora kinases are promising targets in the search for new anticancer drugs, highlighting Aurora B. Other enzyme related to tumoral processes is the tyrosine kinase FLT3 and closely related to the acute myeloid leukemia (AML). FLT3 enzyme is expressed in membranes of precursor hematopoietic cells and have important role in cellular differentiation, proliferation and multiplication. In AML disease, normally, occurs hyperstimulation or mutations of FLT3 enzyme, leading to exacerbated cellular proliferation and lower response to standard cytotoxic agents. FLT3 and dual Aurora B/FLT3 inhibitors have shown relevance in searching for promising new anticancer compounds, mainly to AML. This work was designed to study and understand the interactions between two different targets, Aurora B and FLT3 enzymes, and several indolin-2-one derivatives, structurally similar to sunitinib drug. Molegro Virtual Docker software was utilized in docking estimates and the human Aurora B and FLT3 structures obtained from PDB (4AF3 and 4XUF) with hesperadin and quizartinib used as reference compounds, respectively. The mathematical models, performed in Chemoface program, achieved R 2 of 0.94 and 0.82, suggesting that the binding conformations of the ligands with human Aurora B and FLT3 are reasonable and the data can be used to predict the level of interaction of other Aurora B and FLT3 indolin-2-one inhibitors with similar molecular patterns. Compound 1 showed more stable interaction energies, -225.90 kcal.mol -1 to Aurora B and -233.25 kcal.mol -1 to FLT3, among all studied inhibitors with experimental data available, while sunitinib was the least stable (-135.63 kcal.mol -1 ) considering the Aurora B enzyme and one of the least stable (-160.94 kcal.mol -1 ) to FLT3. Four new proposed indolin-2-one derivatives ... |
| نوع الوثيقة: | thesis |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | FERNANDES, I. A. Molecular docking of Indolin-2-one compounds as promising dual aurora B/FLT3 inhibitors as anticancer agents. 2018. 105 p. Tese (Doutorado em Agroquímica)-Universidade Federal de Lavras, Lavras, 2018.; http://repositorio.ufla.br/jspui/handle/1/32170Test |
| الإتاحة: | http://repositorio.ufla.br/jspui/handle/1/32170Test |
| حقوق: | restrictAccess |
| رقم الانضمام: | edsbas.F6BC59AC |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |