DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OF NARINGENIN DERIVATIVES

Abstract

Naringenin is a flavanoid that belongs to a subclass known as flavanones present in several citrus fruits. It is a primary C15 intermediate in the biosynthesis pathway of flavonoids. It has a wide range of biological activity such as anti-inflammatory, anti-viral, anti-Alzheimer, anti-diabetic, hepatoprotective, and cardio-protective, eye protective, anti-oxidant and anti-cancer activities. Therefore, it is important to identify the mechanisms by which anti-oxidant and anti-cancer activities occur in naringenin because it makes it beneficial in the pharmaceutical industry. The anti-oxidant activity of naringenin is owed to the hydroxyl groups present in the 5th and 7th positions of ring A and 4' of ring B. The activity increased with a double bond between the second and third carbons in the C ring and electron- donating groups at position 3 in ring C. 5, 7 dihydroxy groups can stabilize the structure through resonance. The 4-carbonyl substituent and the 5-hydroxy group in naringenin are able to from complexes with transition metals-preventing the formation of free radicals. Naringenin can be synthesized from naringin by enzymatic hydrolysis using naringinase enzyme. Several derivatives can be synthesized from naringenin such as naringenin O-alkyl derivatives, naringeninoximes and oxime ethers, and the incorporation of biotransformation technology can also produce a number of derivatives. The derivatives are beneficial because they often have more potent biological activity. Our aim is to design new amine derivatives of naringenin, and test the biological activity of these synthesized derivatives against cancer cell lines. These derivatives were synthesized by aldol condensation reaction followed by the nucleophilic addition of different amines. Different spectroscopic methods of analysis, such as 1H NMR and IR spectroscopy, were used for structural characterization of the synthesized derivatives.Biological evaluation of these derivatives is expected to show increased anti-cancer activity in comparison to the parent compound, Naringenin.