Design and Synthesis of Hesperidin Derivatives With Anti-Inflammatory Potential

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Computational Chemistry

Background:

• Hesperidin, a citrus flavonoid, possesses diverse pharmacological activities.
• There is a need for novel anti-inflammatory compounds with improved efficacy.
• Developing new hesperidin derivatives can lead to potent therapeutic agents.

Purpose of the Study:

• To design and synthesize novel hesperidin derivatives.
• To evaluate the anti-inflammatory potential of these derivatives.
• To investigate the molecular interactions of promising compounds.

Main Methods:

• Synthesis of 22 hesperidin derivatives incorporating fatty and cinnamic acid groups.
• Assessment of inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 macrophages.
• Molecular docking simulations with the NLRP3 protein and quantum chemical calculations.

Main Results:

• Compound B8 exhibited the most potent inhibition of NO production (IC50 = 10.4 ± 0.7 µM) without significant cytotoxicity.
• Molecular docking revealed a favorable binding energy of -8.39 kcal/mol for compound B8 with the NLRP3 protein.
• Quantum chemical calculations provided insights into the binding interactions.

Conclusions:

• The synthesized hesperidin derivatives, particularly B8, show significant anti-inflammatory potential.
• Compound B8 represents a promising lead for the development of novel anti-inflammatory drugs.
• The study offers a valuable structural design strategy for future hesperidin-based drug discovery.