• Refine Query
  • Source
  • Publication year
  • to
  • Language
  • 1
  • 1
  • 1
  • 1
  • 1
  • 1
  • 1
  • 1
  • Tagged with
  • 3
  • 2
  • 1
  • 1
  • 1
  • 1
  • 1
  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

The hydroxylamino derivatives of santonin.

Davis, Michael Jessop. January 1967 (has links)
No description available.
2

The hydroxylamino derivatives of santonin.

Davis, Michael Jessop. January 1967 (has links)
No description available.
3

AvaliaÃÃo do potencial citotÃxico de trÃs novos derivados da a-santonina em modelos experimentais in vitro / Evaluation of the cytotoxic potential of three new derivatives of α-santonin in experimental models

Josà Roberto de Oiveira Ferreira 26 March 2009 (has links)
Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / As lactonas sesquiterpÃnicas apresentam estruturas quÃmicas diversificadas, bem como uma grande variedade de atividades biolÃgicas, dentre as quais se destaca a atividade citotÃxica e antitumoral. O objetivo do presente trabalho foi avaliar o potencial citotÃxico de trÃs novos derivados da α-santonina (1): 3-oxo-7αH,6H-eudesma-1,4,11-trien-6,12-olideo (2), 11,13-dehidrolumissantonina (3) e 10α-acetoxi-3-oxo-1,7αH,6H-guai-4,11-dien-6,12-olideo (4) e estudar seus efeitos sobre a proliferaÃÃo celular, ciclo celular e eventos apoptÃticos. Todos os novos derivados inibiram a proliferaÃÃo das cÃlulas tumorais, pelo ensaio do MTT, exceto o protÃtipo (α-santonina), apÃs 72 h de incubaÃÃo. As linhagens HL60 (leucemia) e HCT-8 (cÃlon) mostraram maior sensibilidade ao tratamento com os novos derivados, cujos valores de CI50 para HL60 foram 1,14 (0,23-2,77); 2,30 (1,87-2,84) e 1,60 (1,09-2,35) ÂM e HCT-8 iguais a 2,92(0,98-4,86); 1,96 (1,64-2,29)e 0,36 (0,16-0,79) ÂM, para os compostos 2, 3 e 4, respectivamente. Dois dos trÃs derivados foram menos citotÃxicos para as cÃlulas mononucleares do sangue perifÃrico (PBMC) com CI50 igual a 10,75 (4,6-23,3) ÂM (3) e CI50 igual a 16,77 (7,3-36,8) ÂM (4). PorÃm, o composto 2 apresentou menor seletividade (CI50 igual a 3,24 (1,6-5,3) ÂM) em relaÃÃo as cÃlulas nÃo tumorais. Nenhum dos compostos estudados induziu efeitos hemolÃticos. Para estudo do mecanismo de aÃÃo foi escolhida a linhagem HL-60 como modelo experimental. Culturas de HL60 foram tratadas com os derivados (1 e 2 ÂM) por 24 h. Todos os derivados foram capazes de reduzir o nÃmero de cÃlulas viÃveis, avaliado pelo ensaio de exclusÃo do azul de tripan, na maior concentraÃÃo testada, sem induzir aumento na incidÃncia de cÃlulas nÃo viÃveis. A aÃÃo antiproliferativa esta relacionada com a capacidade de inibir a sÃntese de DNA. ApÃs o tratamento, os derivados foram capazes de induzir apoptose, como observado pelo padrÃo de morfologia celular: presenÃa de condensaÃÃo de cromatina e fragmentaÃÃo nuclear, bem como por citometria de fluxo (manutenÃÃo da integridade de membrana plasmÃtica, fragmentaÃÃo do DNA, externalizaÃÃo da fosfatidilserina e ativaÃÃo de caspases 3 e 7). Nenhum dos derivados causou despolarizaÃÃo da membrana mitocondrial, sugerindo a participaÃÃo da via extrÃnseca no processo apoptÃtico. Os compostos 3 e 4 foram capazes de causar acÃmulo de cÃlulas na fase G2/M do ciclo celular, indicando um mecanismo de aÃÃo diferenciado em relaÃÃo ao composto 2. Esses dados sugerem que os derivados da α-santonina avaliados no presente estudo apresentam um potencial anticÃncer, em especial o composto 4 pela moderada toxicidade em PBMC e por ser capaz de induzir uma maior taxa de morte celular via apoptose quando comparado aos demais derivados estudados. / The sesquiterpene lactones have different chemical structures, and a variety of biological activities, among which stand out the cytotoxic and antitumour activities. The aim of the present study was to determine the cytotoxic effects of three new α-Santonin (1) derivatives: 3-oxo-7αH,6H-eudesma-1,4,11-trien-6,12-olide (2), 11,13-dehydrolumissantonin (3) and 10α-acetoxi-3-oxo-1,7αH,6H-guai-4,11-dien-6,12-olide (4) and study your effects on cell proliferation, cell cycle, and apoptosis events. All new derivatives inhibited the proliferation of tumor cells, by MTT assay, except the prototype (α-santonina) after 72 h of incubation. The cell lines HL60 (leukemia) and HCT-8 (colon) showed greater sensitivity to treatment with these derivatives, with values of IC50 for HL60 equal to 1.14 (0.23-2.77); 2.30 (1.87-2.84) and 1.60 (1.09-2.35) ÂM and for HCT-8 equal to 2.92(0.98-4.86); 1.96 (1.64-2.29) and 0.36 (0.16-0.79) ÂM for compounds 2, 3 and 4, respectively.. Two derivatives were less cytotoxic to peripheral blood mononuclear cells (PBMC): IC50 equal to 10.75 (4.6-23.3) ÂM (3) and IC50 equal to 16.77 (7.3-36.8) ÂM (4). However, compound 2 showed lower selectivity (IC50 equal to 3.24 (1.6-5.3) ÂM) on PBMC. None of the studied compounds induced hemolytic effects. To evaluate the mechanism of action promoted by these derivatives, HL60 cells was chosen as an experimental model, since this linage was one of the most sensitive to treatment. HL60 cultures were treated with α-santonin derivatives (1 and 2 ÂM) during 24 h. All compounds were able to reduce the number of viable cells evaluated by the trypan blue dye exclusion test at highest concentration, without increasing the number of non-viable cells. The antiproliferative action is related to the ability to inhibit the synthesis of DNA. After treatment, the derivatives were able to induce apoptosis, as observed by cell morphology pattern (chromatin condensation, and nuclear fragmentation), and by flow cytometry (membrane integrity, DNA fragmentation, anexin positive cells, and caspases 3 and 7 activation). None of all derivatives analyzed caused depolarization of mitochondrial membrane, suggesting the involvement of the extrinsic pathway in the apoptotic process. The compounds 3 and 4 induce G2/M cell cycle arrest, indicating a different mechanism of action in relation to compound 2. These data suggest that α-santonin derivatives evaluated in the present study showed a anticancer potential, especially the compound 4, which induced moderate toxicity on PBMC, in addition this compound induced a higher rate of cell death via apoptosis when compared to the other α-santonin derivatives evaluated.

Page generated in 0.0521 seconds