Synthesis of new fatty acid synthase inhibitors with cytotoxic properties

Cancer is one of the diseases with the highest rates of mortality, its treatment is normally extremely painful and full of unwanted side-effects. One enzyme that is commonly overexpressed in many cancer cells, is the fatty acid synthase (FAS). FAS is considered a target for cancer treatment; many FAS inhibitors have shown a potent cytotoxic effect with minimal damage to normal cells. C75 is a well-known FAS inhibitor that has strong cytotoxic effects in mice but also has anorexic side-effects. Further studies determined that the (-)-C75 enantiomer has strong cytotoxic effects without affecting the food intake and body weight. Therefore, it was developed a (-)-C75-based inhibitor with better cytotoxic effects in several cell lines, the compound (-)-UB006. This inhibitor showed to be very potent in micromolar ranges, but it is necessary to develop new analogs with stronger cytotoxic effects in nanomolar ranges. In the present work, precursors of the (±)-UB006 and a nitrogenated analog were synthesized in high amounts by conventional organic synthesis. A new methodology to obtain the nitrogenated analog of (±)-UB006 was performed, which turned out to be very problematic and therefore unsuccessful. Moreover, the scaling-up of the overall synthesis of nitrogenated analog of (±)- UB006 showed that both reaction yield and purity were negatively affected by the increase in the amount of crude to be purified. Finally, the compounds obtained in this work will be used in further synthetic steps for the obtention of new FAS inhibitors.

• Main Author: Montesdeoca Solórzano, Nicolás Alejandro (author)
• Format: bachelorThesis
• Language: eng
• Published: 2020
• Subjects: Cáncer; Lípidos; Ácidos grasos; Encima FAS; Inhibidor de FAS; Propiedades citotóxicas; Síntesis orgánica; Escalado; Lipids; Fatty acids; Cytotoxic properties; Organic synthesis; Scale-Up
• Online Access: http://repositorio.yachaytech.edu.ec/handle/123456789/138