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Inositol monophosphatase 2 (IMPase 2) and its inhibition by LITHIUM(l) and hesperetin

Grant number: 20/04488-1
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): September 01, 2020
Effective date (End): August 31, 2021
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Organic Chemistry
Principal Investigator:Ljubica Tasic
Grantee:Rafaella Trevisan Scandiuzzi
Home Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Bipolar disorder (BD) is characterized by a sudden change in mood, which alternates between euphoria and depression, and it is not uncommon for its carriers to end their life with suicide. In Brazil, there are about 6 million people diagnosed with BD. Lithium(I) is a medication used to relieve BD symptoms along with other therapies, whose medicinal dose is very close to toxic and its beneficial effects on BD patients are below 60%. With the use of this treatment, a decrease in myo-inositol was observed in patients, compared with BD patients who did not use lithium(I) as therapy. Thus, an important connection between bipolar disorder and the altered performance of enzymes of the family of inositol monophosphatases (IMPases) was proposed, especially from IMPase 2, which became a target for the design of new drugs. Our project aims to propose a flavone, hesperetin, as a possible phytotherapeutic for BD and an inhibitor of IMPase 2. In silico tests and preliminary experiments conducted in vitro proved the potential inhibitory effect of hesperetin against IMPase 2. To test the interaction of hesperetin with IMPase 2, we propose the application of biophysical and biochemical techniques, such as fluorescence assays and enzymatic activity tests. It is expected to verify and later describe the action of hesperetin, as well as to compare the effects of lithium(I) with the effects of hesperetin to IMPase 2.