Research Information System
Görgülü A. O. (Executive), Danış Ö., Koran K., Çalışkan E., Meletli F., Dicle C., et al.
Project Supported by Higher Education Institutions, BAP Research Project, 2024 - 2026
The type, number, and properties of functional groups carried by phosphazene rings allow for the design and synthesis of various molecular materials. Therefore, depending on the properties of various substituents attached to phosphazene rings, they exhibit numerous biological properties.
Cinnamic acid (C9H8O2), known as 3-phenyl-2-propenoic acid, which is an important component of the plant Cinnamomum cassia from the Lauraceae family, has a white and crystalline structure and is commonly found in sweet compositions and cinnamon oil. Cinnamic acid and its derivatives are compounds widely found in vegetables, fruits, and flowers. Cinnamic acid has various pharmacological properties, especially antioxidant activity. Phosphazene compounds exhibit significant physical and chemical properties depending on the properties of the organic or inorganic substituents attached to their structure. Therefore, considering the demand for new and innovative drug molecules in the medical field in recent years, the importance of phosphazene compounds is great. Briefly, new structures obtained by combining cyclophosphazene, N-phenol, and its derivatives offer valuable potential in MAO enzyme inhibitor studies. New cyclophosphazene structures containing a biphenol-linked phosphazene ring in the molecular center and hydroxysinnamic acid derivatives containing amino acids in the side groups, which do not exist in the literature, will be synthesized and characterized. These new spirocyclophosphazenes aim to inhibit MAO enzymes, which are effective in Parkinson's disease.
First, three cinnamic acid compounds (HCA, HMCA, HNtCA) will be synthesized using 4-hydroxybenzaldehyde, 4-hydroxy-3-methoxybenzaldehyde, and 4-hydroxy-3-nitrobenzaldehyde. Subsequently, N-phenol amino acid derivatives will be obtained by reacting these cinnamic acids with amino acid methyl esters.
Then, six N-phenol amino acid derivatives (HCA-Ala-OCH3, HMCA-Ala-OCH3, HNtCA-Ala-OCH3, HCA-Phe-OCH3, HMCA-Phe-OCH3, HNtCA-Phe-OCH3) will be obtained by reacting these cinnamic acid derivatives with amino acid methyl esters.
Later, new cyclophosphazene compounds (DFF-HCA-Ala-OCH3, DFF-HMCA-Ala-OCH3, DFF-HNtCAAla-OCH3, DFF-HCA-Phe-OCH3, DFF-HMCA-Phe-OCH3, DFF-HNtCA-Phe-OCH3) will be obtained as a result of the reactions of spirocyclophosphazene (DFF) compound with N-phenol amino acid derivatives. The structures of all compounds will be characterized by FT-IR, NMR, and mass spectroscopy.
Finally, the effects of these compounds, which will be synthesized and characterized, on human MAO-A and MAO-B activities will be determined spectrofluorometrically, and the inhibition mechanisms of compounds exhibiting high inhibitory activity will be investigated in detail. Neurodegenerative disorders are diseases that manifest with advancing age and negatively affect the health and quality of life of these patients. Parkinson's disease is one of the most common neurodegenerative disorders, and although there is no definitive treatment, L-dopa and monoamine oxidase-B (MAO-B) inhibitors are used in its symptomatic treatment. These drugs aim to increase dopamine levels in neurons, which are at the heart of Parkinson's pathophysiology. This study has the potential to provide another drug idea for the quality of life that Parkinson's patients may want.