Design of acyl salicylic acid derivates as COX-1 inhibitors using QSAR approach, molecular docking and QSPR analysis
DOI:
https://doi.org/10.46542/pe.2024.243.8894Keywords:
Acyl salicylic acid, COX-1, Docking, QSAR, QSPRAbstract
Background: Acetylsalicylic acid (aspirin), widely used as an antiplatelet agent, is more likely to inhibit COX-1. Along with discovering the cardioprotective role of COX-1 in controlling platelet aggregation, it is important to develop a selective COX-1 inhibitor.
Objective: This study aims to design acyl salicylic acid derivatives intended as COX-1 inhibitors.
Method: Fourteen derivatives (AcS1-14) were subjected to a quantitative structure-activity relationship (QSAR) study, and 31 QSAR models were obtained using multiple linear regression (MLR) analysis. Molecular docking was performed on COX-1 (PDB. 1PTH) using the Molecular Orbital Environment (MOE) program ver2022.02, and QSPR analysis was conducted to ascertain the contribution of physicochemical descriptors to the free energy score (S) of ligand-receptor complexes.
Results: The QSAR-Hansch model predicted hydrophobicity (LogP) and molecular energy (Etotal) and contributed to pain inhibitory action. All derivatives displayed higher in silico affinity than aspirin (S= -4.33±0.00 kcal/mol), and compound AcS7 afforded the highest (S= -5.32 kcal/mol). In QSPR, Etotal also revealed a positive contribution to the affinity. AcS1, AcS2, AcS5, AcS7, and AcS8 expressed higher drug-like properties than aspirin.
Conclusion: Derivatives with optimum hydrophobicity and high energy would generate potent COX-1 inhibition. The five selected compounds were recommended to be developed as drug candidates for COX-1 inhibitors.
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