Alessandra Ammazzalorso
University of Chieti, Italy
Title: Synthesis and cytotoxicity evaluation of novel amide and sulfonimide PPARaï¡ antagonists
Biography
Biography: Alessandra Ammazzalorso
Abstract
Peroxisome Proliferator-Activated Receptors (PPARs) have been widely studied in the last decades, and they attracted the attention of scientists as promising therapeutic targets. Intensive efforts by researchers produced a wide panel of drugs targeting the three PPAR subtypes (PPARï¡, PPARï§, PPARï¤) able to modulate important metabolic functions. PPAR activation is involved in several physiologic pathways, as lipid and glucose metabolism, insulin sensitivity, energy homeostasis, and cell differentiation. Fibrates and thiazolidinediones, respectively synthetic PPARï¡ and PPARï§ agonists, are currently used for the treatment of hyperlipidemia and hyperglycemia, in patients affected by type 2 diabetes and metabolic syndrome. In recent years, an increased expression of PPARï¡ has been found in different tumors: it is well known that cancer cells present altered metabolic pathways, switching from the glycolysis to fatty acid oxidation metabolism. In this scenario, PPARï¡ antagonists emerged as novel potential drugs in tumors overexpressing PPARï¡, by interfering with cellular survival and metastasis formation [1]. In vitro anticancer effects were found for PPARï¡ antagonists in chronic lymphocytic leukemia [2], renal cancer [3], colorectal and pancreatic cancer [4], paraganglioma [5]. In this study we report on the synthesis of novel amide and sulfonimide PPARï¡ antagonists, starting from the structure of PPARï¡ agonists, previously synthesized in our laboratory. Furthermore, we explored the possible cytotoxicity of the novel compounds in different cancer cell lines (colorectal, pancreatic and paraganglioma) expressing PPARï¡