Coumarin-Amino Acid Hybrids Used as Possible Multifactorial Anti-Inflammatory Agents

Area of Science:

• Medicinal Chemistry
• Pharmacology

Background:

• Coumarin derivatives are known for diverse biological activities.
• Amino acid conjugation can modulate pharmacological properties.

Purpose of the Study:

• To synthesize and evaluate novel coumarin-amino acid hybrids.
• To assess their antioxidant and anti-inflammatory potential in vitro.
• To predict their drug-likeness using in silico methods.

Main Methods:

• Synthesis of coumarin-amino acid hybrids.
• In vitro antioxidant assays (AAPH-induced linoleic acid peroxidation).
• In vitro anti-inflammatory assays (Soybean lipoxygenase, Ovine cyclooxygenase-2 inhibition).
• In silico drug-likeness prediction (Molinspiration, SwissADME, etc.).

Main Results:

• Compounds were synthesized in good yields.
• Compound 15 exhibited potent antioxidant activity (93% inhibition).
• Compound 4 was the most effective LOX inhibitor (IC50 = 58 μM).
• Compounds 4 and 5 showed strong COX-2 inhibition (IC50 = 55 μM).
• Compounds 4, 9, and 15 displayed pleiotropic activities.
• In silico analysis revealed favorable drug-like properties (QED > 0.5).

Conclusions:

• Coumarin-amino acid hybrids possess significant antioxidant and anti-inflammatory properties.
• Compound 4 is a promising lead for developing pleiotropic anti-inflammatory agents.
• In silico predictions support the potential therapeutic applications of these compounds.