Development of Fluorescent Aminoquinolines for Determination of the Myeloperoxidase

• Grant number: 24/16838-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2025
• End date: July 31, 2028
• Field of knowledge: Biological Sciences - Biochemistry - Enzymology
• Principal Investigator: Valdecir Farias Ximenes
• Grantee: Maiara Stefanini Borges Caires
• Host Institution: Faculdade de Ciências (FC). Universidade Estadual Paulista (UNESP). Campus de Bauru. Bauru , SP, Brazil
• Associated research grant: 24/00959-0 - Fluorescent and Dichroic Probes: Development of Bioanalytical Methodologies, AP.R

Abstract

Modern biomedical research requires accurate fluorescent markers to study cellular processes, such as signaling pathways and reactive oxygen species (ROS). Fluorescent probes are essential for detecting biomolecules, monitoring enzymatic reactions, and identifying changes in microenvironments. They are sensitive to the physicochemical characteristics of the medium, altering their quantum yield and emission wavelength according to environmental variations, such as polarity and pH. Aminoquinolines, a class of quinolines, have been highlighted in the development of fluorescent probes due to their heterocyclic nucleus and conjugated electronic systems, known for their fluorescent properties and sensitivity to the environment. Myeloperoxidase (MPO) is physiologically expressed in circulating neutrophils, monocytes, and some tissue macrophages. In addition to its essential role in the human antimicrobial system via the production of hypochlorous acid (HOCl), MPO can be released from phagocytes leading to tissue damage during inflammation, thus being a key factor in the pathophysiology of cardiovascular, inflammatory, neurodegenerative, renal and immune-mediated diseases. Therefore, developing probes capable of detecting the involvement of MPO in pathological processes is of great relevance today. The project proposes the synthesis of ami/noquinolines with different substituents, the study of their spectroscopic and solvatochromic properties and the development of a fluorescent methodology for the detection of MPO enzymatic activity and detection of HOCl generated by leukocytes. The hypothesis is that these modified aminoquinolines can serve as selective and sensitive fluorescent probes to detect MPO activity, differentiating several oxidant species, contributing to new enzymatic monitoring tools and advances in the diagnosis and treatment of inflammatory and oxidative diseases.