| Texto completo | |
| Autor(es): Mostrar menos - |
da Costa, Ricardo M.
[1, 2]
;
Bastos, Jairo K.
[3]
;
Costa, Maria C. A.
[4]
;
Ferreira, Marcia M. C.
[4]
;
Mizuno, Cassia S.
[5]
;
Caramori, Giovanni F.
[6]
;
Nagurniak, Glaucio R.
[6]
;
Simao, Marilia R.
[1]
;
dos Santos, Raquel A.
[1]
;
Veneziani, Rodrigo C. S.
[1]
;
Ambrosio, Sergio R.
[1]
;
Parreira, Renato L. T.
[1]
Número total de Autores: 12
|
| Afiliação do(s) autor(es): | [1] Univ Franca Unifran, Nucleo Pesquisa Ciencias Exatas & Tecnol, Franca, SP - Brazil
[2] Informat Aplicada Ciencias IFSULDEMINAS, Muzambinho, MG - Brazil
[3] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Ribeirao Preto, SP - Brazil
[4] Univ Campinas Unicamp, Inst Chem, Theoret & Appl Chemometr Lab LQTA, Campinas, SP - Brazil
[5] Univ New England, Coll Pharm, Dept Pharmaceut Sci, Portland, ME - USA
[6] Univ Fed Santa Catarina, Dept Quim, Campos Univ Trindade, Florianopolis, SC - Brazil
Número total de Afiliações: 6
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Phytochemistry; v. 156, p. 214-223, DEC 2018. |
| Citações Web of Science: | 1 |
| Resumo | |
In this study, ent-kaurenoic acid derivatives were obtained by microbial transformation methodologies and tested against breast cancer cell lines (MCF-7). A multivariate quantitative-structure activity relationship (QSAR) analysis was performed taking into account both microbial transformation derivatives and other analogues previously reported in literature to give some insight into the main features behind the cytotoxic activity displayed by kaurane-type diterpenes against MCF-7 cells. The partial least square regression (PLS) method was employed in the training set and the best PLS model was built with a factor describing 69.92% of variance and three descriptors (logP, epsilon(HOMO) and epsilon(HOMO-1)) selected by the Ordered Predictors Selection (OPS) algorithm. The QSAR model provided reasonable regression (Q(2) = 0.64, R-2 = 0.72, SEC = 0.29 and SEV = 0.33). The model was validated by leave-N-out cross-validation, y-randomization and external validation (R(2)pred = 0.89 and SEP = 0.27). The selected descriptors indicated that the activity was mainly related to electronic parameters (HOMO and HOMO-1 molecular orbital energies), as well as to logP. These findings suggest that higher activity values are directly related with both higher logP and frontier orbital energy values. The positive relationship between these orbitals and the activity suggests that the ent-kaurenoic acid analogues interaction with the target involves charge displacement, which is entirely consistent with the literature. Based on these findings, three compounds were proposed and one of them was synthesized and tested. The experimental result confirmed the activity predicted by the model. (AU) | |
| Processo FAPESP: | 11/13630-7 - Validação química e farmacológica de extratos e princípios ativos de espécies de Copaifera |
| Beneficiário: | Jairo Kenupp Bastos |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 11/23028-2 - Avaliação do potencial biológico de derivados do ácido ent-caurenóico obtidos por biotransformação fúngica e semi-síntese |
| Beneficiário: | Marilia Rodrigues Simão |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado Direto |
| Processo FAPESP: | 07/54762-8 - Obtenção de análogos estruturais do ácido pimaradienóico através do processo de biotransformação fúngica e estudo do efeito destes metabólitos sobre a atividade da enzima TcDHODH e sobre a contração da musculatura lisa vascular de artéria aorta de ratos |
| Beneficiário: | Sergio Ricardo Ambrosio |
| Modalidade de apoio: | Auxílio à Pesquisa - Programa BIOTA - Jovens Pesquisadores |
| Processo FAPESP: | 11/07623-8 - Utilização de métodos mecânicos-quânticos para estudo das ligações e interações químicas em sistemas auto-organizados com aplicação em catálise, química medicinal, eletrocromismo, armazenamento e conversão de energia |
| Beneficiário: | Renato Luis Tame Parreira |
| Modalidade de apoio: | Auxílio à Pesquisa - Jovens Pesquisadores |