Tesis doctoral de Daniel Plano Amatriain
It has been synthesized 71 novel organoselenium compounds with cytotoxic activity in five tumoral cell lines (ccrf-cem, pc-3, htb-54, ht-29 and mcf-7). The most sensitive cell lines to these compounds are pc-3, ccrf-cem and mcf-7. Four compounds are more active, with gi50, tgi and ld50 values lower, than the chemotherapy reference compounds doxorubicine, camptothecin, paclitaxel and metotrexate in mcf-7 cell line. Fifteen compounds show ic50 values lower than reference drugs etoposide, methylseleninic acid and topotecan. it has been studied the biological mechanisms of action for 7 leader compounds, showing that they induce apoptosis in ccrf-cem and mcf-7 cell lines, they affect to cell cycle distribution in mcf-7 cell line, they inhibit the activity of several kinases and some of them are able to increase the selenoprotein p level in an in vitro luminometric assay in hepg2 cell line. the synthesized compounds were characterized by infrared spectroscopy, chn elemental analysis and nuclear magnetic resonance. Moreover, it has been studied the tautomeric equilibrium and the effect of the temperature in this equilibrium for alkyl imidoselenocarbamate derivatives using nmr. Furthermore, it has been performed a thermal analysis for these derivatives using thermogravimetry and differential scanning calorimetry. These compounds present an interesting polymorphic behavior. Finally, it has been performed x-ray diffraction assays in powder and monocrystal for two and one compounds, respectively. it has been started some collaboration with other research groups of the university of navarra (spain), the university of alcala (spain) and the texas tech university (eeuu). In these studies, it has been evaluated the inhibition of angiogenesis in vitro, the leishmanicidal activity in promastigotes and amastigotes of leishmania infantum and the generation of superoxides in vitro.
Datos académicos de la tesis doctoral «Diseño, síntesis y evaluación biológica de nuevos compuestos organoselénicos con actividad citotóxica y apoptótica«
- Título de la tesis: Diseño, síntesis y evaluación biológica de nuevos compuestos organoselénicos con actividad citotóxica y apoptótica
- Autor: Daniel Plano Amatriain
- Universidad: Navarra
- Fecha de lectura de la tesis: 17/06/2010
Dirección y tribunal
- Director de la tesis
- Juan Antonio Palop Cubillo
- Tribunal
- Presidente del tribunal: rosa María Claramunt vallespí
- José ignacio Borrell bilbao (vocal)
- lutz Schomburg (vocal)
- Francisco Palacios gambra (vocal)