• Universitat de València
• INCLIVA Institute for Health Research

• Ainhoa Natividad García Martín
• Álvaro Bernabéu Sanchis
• Nuria Cabedo Escrig
• Carlos Luís Villarroel Vicente
• Laura Vila Dasí
• Martínez Solsona

Metabolic syndrome (MS) is defined by the simultaneous presence of a cluster of cardiovascular risk factors and is associated with the development of type 2 diabetes, dyslipidaemias, cardiovascular disease and non-alcoholic fatty liver disease, among others. Furthermore, there is evidence that MS is associated with systemic inflammation, which appears to be the main trigger for its complications.

In recent years, numerous therapeutic modalities have emerged for the treatment metabolic disorders such as MS, based on the selective activation of peroxisome proliferator-activated receptor agonists (PPAR-alpha and PPAR-gamma). For example, fibrates, which are agonists of the PPAR-alpha receptor, are used to treat dyslipidaemias, including hypertriglyceridaemia and other forms of hyperlipidaemias. Thiazolidinediones, also known as glitazones, are agonists of the PPAR-gamma receptor and are used in the treatment of type 2 diabetes. However, the limited effect of PPAR-alpha agonists on glucose metabolism and the side effects associated with selective PPAR-gamma activators (including an increased risk of cardiovascular disease, hepatotoxicity and bladder cancer) have necessitated the development of new dual PPAR-alpha/gamma or pan-PPAR agonists, with partial activity on PPAR-gamma.

A team of researchers from the Universitat de València and INICLIVA have developed a series of compounds based on tetrahydroquinolines and quinolines with pan-PPAR activity. These compounds have been shown to:

• support lipid metabolism and reduce inflammation in metabolic disorders, which may prevent the development of cardiovascular complications;
• improve lipid and carbohydrate parameters in obese and diabetic mice.

This invention could have potential applications in field of pharmacology, with the possibility of the improving outcomes in the treatment of various cardiometabolic and vascular pathologies, including type 2 diabetes, hypertriglyceridaemia, non-alcoholic fatty liver disease and neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease.

The primary advantages of this invention are:

• improvement in the treatment of metabolic and neurodegenerative diseases, reducing the toxicity and side effects that result from lower PPAR-gamma activity in comparison to other agonists;
• administration of a single medication to control metabolic alterations and inflammation, eliminating the need to take complementary drugs with their consequent side effects and adherence to treatment.

• Patent applied