Synthesis of chromone carboxamide derivatives with antioxidative and calpain inhibitory properties

Area of Science:

• Biochemistry
• Medicinal Chemistry
• Neuroscience

Background:

• Overactivation of μ-calpain contributes to cell damage in various diseases.
• Cell death in neurodegenerative disorders is associated with reactive oxygen species (ROS) overproduction.
• Antioxidants and μ-calpain inhibitors represent potential therapeutic strategies for cell death-related conditions.

Purpose of the Study:

• To synthesize novel chromone carboxamide derivatives as potential μ-calpain inhibitors.
• To evaluate the μ-calpain inhibitory and antioxidant activities of the synthesized compounds.
• To identify compounds with therapeutic potential for diseases involving μ-calpain overactivation and oxidative stress.

Main Methods:

• Synthesis of new chromone carboxamide derivatives (Compounds 3).
• Assay of μ-calpain inhibitory activity (IC50 values).
• Evaluation of antioxidant properties using DPPH scavenging and lipid peroxidation inhibition assays.

Main Results:

• Compounds 3h and 3l displayed potent μ-calpain inhibitory activity (IC50=0.09-0.10 μM), comparable to reference compound 2 (IC50=0.07 μM).
• Compound 3i exhibited significant μ-calpain inhibition (IC50=0.28 μM) alongside notable antioxidant activities.
• The synthesized derivatives offer alternative therapeutic options targeting μ-calpain overactivation.

Conclusions:

• Novel chromone carboxamide derivatives effectively inhibit μ-calpain.
• Compound 3i possesses both μ-calpain inhibitory and antioxidant capabilities, suggesting dual therapeutic potential.
• These findings support the development of new treatments for neurodegenerative and other cell death-related diseases.