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Alessandra Ammazzalorso

Alessandra Ammazzalorso

University of Chieti, Italy

Title: Synthesis and cytotoxicity evaluation of novel amide and sulfonimide PPARa 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 (PPAR, PPAR, PPAR) 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 PPAR and PPAR 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 PPAR 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, PPAR antagonists emerged as novel potential drugs in tumors overexpressing PPAR, by interfering with cellular survival and metastasis formation [1]. In vitro anticancer effects were found for PPAR 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 PPAR antagonists, starting from the structure of PPAR 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 PPAR