Integrated Approach towards Potential Therapeutic Agent for Inflammation-Mediated CVD Utilizing Computational and...

Area of Science:

• Medicinal Chemistry
• Computational Chemistry
• Pharmacology

Background:

• Chronic inflammation is a key driver of cardiovascular diseases (CVDs), necessitating novel therapeutic strategies.
• Existing treatments for inflammation-related CVDs have limitations, highlighting the need for new drug candidates.

Purpose of the Study:

• To synthesize and characterize N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-6-nitrobenzo[d][1,3]dioxole-5-carboxamide (EMC) as a potential therapeutic agent for inflammation-related CVDs.
• To evaluate EMC's physicochemical properties, pharmacokinetic profile, and inhibitory activity against cyclooxygenase-2 (COX-2).

Main Methods:

• Density Functional Theory (DFT) for physicochemical properties, including energy gap (ΔE = 2.97 eV).
• Hirshfeld surface analysis and Molecular Electrostatic Potential (MEP) for crystal packing and charge distribution.
• Swiss ADME and pkCSM for pharmacokinetic predictions; molecular docking for COX-2 inhibition analysis.

Main Results:

• EMC exhibited favorable drug-like properties and predicted good pharmacokinetics.
• Molecular docking revealed selective COX-2 inhibition with a score of -8.02 kcal/mol, involving key amino acid residues.
• EMC demonstrated antioxidant activity with IC50 values of 21.56 ± 3.99 μM (ABTS) and 41.9 ± 5.17 μM (DPPH).

Conclusions:

• EMC is a promising candidate for treating inflammation-related CVDs due to its selective COX-2 inhibition and antioxidant properties.
• The study provides a foundation for further in vitro and in vivo investigations of EMC's therapeutic potential in cardiovascular conditions.