The Design and Synthesis of Autotaxin Inhibitors and Analogs of Lysophosphatidic Acid

Lysophosphatidic acid (LPA) is a naturally occurring bioactive phospholipid. It has a wide array of biological effects like cell proliferation, survival, migration, apoptosis invasion, wound healing and angiogenesis. Autotaxin (ATX) was identified as an autocrine tumor cell motility factor from A2058 melanoma conditioned medium. ATX has lysophospholipase D enzyme activity and is responsible for the cleavage of lysophophatidylcholine (LPC) leading to the generation of LPA. Antagonists of Autotaxin would have a potential therapeutic application in cancer research. Chapter 1 is an introduction of LPA and autotaxin. It provides the background and significance of the research. Chapter 2 explores the synthesis of the stereoisomers of 3‑CCPA and the pharmacological activites of these isomers. Chapter 3 discusses the design and synthesis of benzyl and naphthalene-methyl phosphonic acid inhibitors of autotaxin with anti‑invasive and anti-metastatic actions. Chapter 4 elaborates on the search for new non‑lipid, drug like LPA analogs. Chapter 5 provides an overview of the work detailed in the dissertation; as well as future directions that will help further the scope of these projects

Database development and machine learning classification of medicinal chemicals and biomolecules

Ph.DDOCTOR OF PHILOSOPH

Screening virtual basado en topología molecular: una nueva metodología en el descubrimiento de agentes anticonvulsivos

La presente tesis se dividirá en dos partes. La primera de ellas, de carácter introductoria, versará sobre las motivaciones y los fundamentos del trabajo de tesis, describiendo la epilepsia y el estado actual de su terapéutica y proporcionando el marco teórico para comprender las bases y los alcances de los estudios QSAR, la Topología Molecular y las técnicas de Screening Virtual (SV). En la segunda se expondrán los resultados obtenidos mediante aplicación de estas metodologías en la búsqueda de nuevos fármacos anticonvulsivos.Facultad de Ciencias Exacta

Proceedings of the 18th Irish Conference on Artificial Intelligence and Cognitive Science

These proceedings contain the papers that were accepted for publication at AICS-2007, the 18th Annual Conference on Artificial Intelligence and Cognitive Science, which was held in the Technological University Dublin; Dublin, Ireland; on the 29th to the 31st August 2007. AICS is the annual conference of the Artificial Intelligence Association of Ireland (AIAI)