Development of lipid and carbohydrate metabolism modulators as potential therapeutic and/or diagnostic agents

The present PhD thesis focuses on the development of novel chemical compounds designed to modulate cellular metabolism for potential therapeutic applications. The rationale behind this research lies in the growing recognition that many pathological conditions, particularly cancer, are driven by modifications in cellular metabolism that enhance disease progression. By selectively modulating these metabolic pathways, it may be possible to disrupt disease progression and improve therapeutic outcomes in a wide range of pathologies. This thesis specifically focuses on two molecular targets that are integral to the metabolic adaptations observed in several pathological states, making them attractive therapeutic targets: CD36, a key fatty acid transporter involved in lipid metabolism, and monoacylglycerols lipase (MAGL), an enzyme responsible for lipid degradation and endocannabinoid system regulation. Both CD36 and MAGL are particularly relevant in the context of cancer and metabolic disorders, as well as individually in several other pathologies. Following a general introduction to cellular metabolic reprogramming in cancer cells and an overview of the endocannabinoid system, this thesis will examine these two targets in detail. The research will explore their roles in cellular metabolism, the pathways they influence, and how their dysregulation contributes to diseases. In addition, the thesis will discuss the design, synthesize, and evaluation of novel chemical compounds aimed at modulating the activity of CD36 and MAGL, with the goal of identifying promising therapeutic agents to expand the pharmacological therapies available.