Detalhes bibliográficos
| Ano de defesa: |
2021 |
| Autor(a) principal: |
AGUIAR, Deivson Ferreira
 |
| Orientador(a): |
OLIVEIRA, Ronaldo Nascimento de |
| Banca de defesa: |
CAMARA, Celso de Amorim,
SOUZA FILHO, Luis Gustavo de,
ARAÚJO, Elmo Silvano de,
SANTOS, Renata Francisca da Silva |
| Tipo de documento: |
Tese
|
| Tipo de acesso: |
Acesso aberto |
| Idioma: |
por |
| Instituição de defesa: |
Universidade Federal Rural de Pernambuco
|
| Programa de Pós-Graduação: |
Programa de Pós-Graduação em Desenvolvimento e Inovação Tecnológica em Medicamentos
|
| Departamento: |
Departamento de Ciências Moleculares
|
| País: |
Brasil
|
| Palavras-chave em Português: |
|
| Área do conhecimento CNPq: |
|
| Link de acesso: |
http://www.tede2.ufrpe.br:8080/tede2/handle/tede2/8994
|
Resumo: |
Heterocyclic compounds are present in numerous drugs. Heterocycles such as oxadiazole and imidazole have contributed to the development of new drugs with possible applications such as antiviral, antitumoral, anti-inflammatory and antimicrobial. In this work we propose the synthesis of a molecular diversity of 1,2,4-oxadiazoles and imidazol-naphthoquinones and evaluate their cytotoxic and antitumor potential. O-Acylamidoximes (3a-k) were synthesized via reaction of arylamidoximes (1a-k) with 1-adamantanecarbonyl chloride. Then, cyclocondensation of the O-acylamidoximes employing various methodologies provided the 1,2,4-oxadiazoles (4a-k). For the synthesis of N'-hydroxy-carboximidamide-2-amino-1,4-naphthoquinones (7a,c,f) and (8a-j) was used the reaction between 2-bromo-1,4-naphthoquinone (5) or to 2,3-dibromo-1,4-naphthoquinone (6) with the arylamidoximes (1a-j). In vitro cytotoxic assays were performed in Vero cells and murine fibroblasts, and in tumor cell lines: prostate adenocarcinoma, acute promyelocytic leukemia, colorectal carcinoma, glioblastoma, chronic and acute myeloid leukemia. O-Acylamidoximes (3a-k) were obtained in moderate-to-good yields (50-80%). The 1,2,4-oxadiazoles (4a-k) were obtained from 52 to 90% of yields. N'-hydroxy-carboximidamide-2-amino-1,4-naphthoquinones were synthesized in yields from 36 to 72% (7a,c,f) and from 47 to 82% (8a-j). In cytotoxic assays in Vero cells, 1,2,4-oxadiazoles were less toxic than O-acylamidoximes, having the compound 4g CC50 = 1797.0 μM. In assays with tumor cell lines, O-acylamidoximes (3a,d-h) showed a selective activity against leukemic cells. For acute promyelocytic leukemia (HL-60) cells, the tested compounds showed an inhibition above 90% at concentrations of 10 μg/ml and 25 μg/ml, and the compound 3e was the most active with IC50 = 19.50 μM for chronic myeloid cells (K562). |
