Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/53889
Title: Synthesis of new heteropolycyclic compounds with potential antitumor activity = Preparació de nous compostos fenólics i derivats amb potencial activitat antitumoral
Author: Soucek, Richard
Director: Pujol Dilmé, M. Dolors
Keywords: Antitumor agents
KRAS
Medicaments antineoplàstics
Síntesi de fàrmacs
Fenols
Antineoplastic agents
Drug synthesis
Phenols
Issue Date: 28-Jan-2014
Publisher: Universitat de Barcelona
Abstract: [spa] El estudio trata de la síntesis y la actividad biológica de 4 antitumorales diferentes: Análogos de tetrahidro-[1,4]-dioxanisoquinolinas, de combretastatina A-4, de dioxancarbazol y del resveratrol. El estudio describe la estrategia sintética y la síntesis multietapas de esos compuestos potencialmente antitumorales. Varias tetrahidroisoquinolinas fueron sintetizadas, cinco de ellas fueron probadas biológicamente y presentan una actividad de inhibición de la proteína K-Ras prometedora. Dos de esos compuestos presentan una actividad anti antiangiogénica elevada y uno presenta actividades de antiosteoporosis. Dos derivados de pirazolona fueron sintetizados y probados biológicamente, uno de ellos muestra una inhibición muy elevada de la K-Ras, de antiangiogénesis y de antiosteoporosis e inhibe la fase G2 del ciclo celular y sus subfases. Se han preparado dos derivados de azolediona combretastatina A-4 que se evaluarán biológicamente. Se sintetizaron dos derivados de dioxancarbazol, uno de ellos presenta una actividad alta de la K-Ras y de antiangiogénesis. Finalmente, se prepararon y evaluaron biológicamente cuatros análogos del resveratrol. Los resultados biológicos muestran una inhibición moderada y selectiva de la K-ras en las líneas celulares estudiadas. Próximamente, el resto de los compuestos sintetizados se evaluarán biológicamente. Ensayos adicionales de inhibición de CDKs, de topoisomerasa II y de toxicidad serán llevados a cabo.
[eng] The study deals with the synthesis and biological activity of 4 different antitumours: Tetrahydro-[1,4]-dioxanisoquinolines, combretastatin A-4, dioxancarbazoles and resveratrol analogues. This study describes the synthesis strategy and multi-step synthesis of these potential antitumour compounds. Various tetrahydroisoquinolines were synthesized, five of which were biologically tested and have a promising K-Ras inhibition activity. Two of them show a high antiangiogenesis activity, one of which also presents antiosteoporosis properties. Two pirazolone derivatives were synthetized and biologically tested, one of which shows a very high K-Ras inhibition, antiangiogenesis and antiosteoporosis activity and inhibits the G2 cell cycle phases and subphases. Two azoledione combretastatin A-4 derivatives were also synthesized and will be biologically tested. Two dioxancarbazoles were prepared and biologically tested, one of which shows a high K-Ras and angiogenesis inhibition. Finally, four resveratrol analogues were synthesized and biologically tested. Their biological results show a moderate and selective K-Ras inhibition on the studied cell lines. In the future, the rest of the synthesized compounds are to be biologically tested. Further CDKs and topoisomerase II inhibition trials as well as toxicity studies will be carried out.
URI: http://hdl.handle.net/2445/53889
Appears in Collections:Tesis Doctorals - Departament - Farmacologia i Química Terapèutica

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